Patient & Survivor Care

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don’t think they’re quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be “practice-changing” for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy “may have resulted in a reduced rate of invasive cancer in the active monitoring group,” the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, “I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

 

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

“The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation,” the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don’t think they’re quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be “practice-changing” for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy “may have resulted in a reduced rate of invasive cancer in the active monitoring group,” the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, “I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

 

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

“The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation,” the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don’t think they’re quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be “practice-changing” for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy “may have resulted in a reduced rate of invasive cancer in the active monitoring group,” the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, “I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

 

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

“The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation,” the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the immune checkpoint inhibitor cosibelimab (Unloxcyt; Checkpoint Therapeutics) for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. 

The programmed death ligand-1 (PD-L1)–blocking antibody is the first and only treatment of its kind approved for advanced CSCC, according to a Checkpoint Therapeutics press release. The FDA approval was based on findings from the multicenter, open-label Study CK-301-101 trial of 109 patients. 

In that trial, the objective response rate (ORR) was 47% in 78 patients with metastatic CSCC and 48% in 31 patients with locally advanced CSCC. Median duration of response (DOR) in treated patients was not reached in those with metastatic disease and was 17.7 months in those with locally advanced disease, according to the FDA approval notice.

Adverse reactions occurring in at least 10% of patients included fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.

The recommended treatment dose, according to the prescribing information, is 1200 mg given as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.

The agent offers “a differentiated treatment option versus available therapies by binding to PD-L1, rather than programmed death receptor-1 (PD-1), to release the inhibitory effects of PD-L1 on the anti-tumor immune response,” Checkpoint Therapeutics president and chief executive officer James Oliviero stated in the company press release. 

The agent has also “demonstrated the ability to induce antibody-dependent cell-mediated cytotoxicity, another potential differentiating feature of the drug compared to existing marketing therapies for CSCC,” Oliviero noted.

“CSCC is the second most common form of skin cancer, and those diagnosed with advanced disease that has recurred or metastasized face a poor prognosis,” stated Emily Ruiz, MD, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital and director of the High-Risk Skin Cancer Clinic at Dana-Farber Brigham Cancer Center. 

“With its dual mechanisms of action and compelling safety profile, this promising drug will provide US oncologists with an important new immunotherapy option for the treatment of CSCC,” she added. 

 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the immune checkpoint inhibitor cosibelimab (Unloxcyt; Checkpoint Therapeutics) for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. 

The programmed death ligand-1 (PD-L1)–blocking antibody is the first and only treatment of its kind approved for advanced CSCC, according to a Checkpoint Therapeutics press release. The FDA approval was based on findings from the multicenter, open-label Study CK-301-101 trial of 109 patients. 

In that trial, the objective response rate (ORR) was 47% in 78 patients with metastatic CSCC and 48% in 31 patients with locally advanced CSCC. Median duration of response (DOR) in treated patients was not reached in those with metastatic disease and was 17.7 months in those with locally advanced disease, according to the FDA approval notice.

Adverse reactions occurring in at least 10% of patients included fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.

The recommended treatment dose, according to the prescribing information, is 1200 mg given as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.

The agent offers “a differentiated treatment option versus available therapies by binding to PD-L1, rather than programmed death receptor-1 (PD-1), to release the inhibitory effects of PD-L1 on the anti-tumor immune response,” Checkpoint Therapeutics president and chief executive officer James Oliviero stated in the company press release. 

The agent has also “demonstrated the ability to induce antibody-dependent cell-mediated cytotoxicity, another potential differentiating feature of the drug compared to existing marketing therapies for CSCC,” Oliviero noted.

“CSCC is the second most common form of skin cancer, and those diagnosed with advanced disease that has recurred or metastasized face a poor prognosis,” stated Emily Ruiz, MD, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital and director of the High-Risk Skin Cancer Clinic at Dana-Farber Brigham Cancer Center. 

“With its dual mechanisms of action and compelling safety profile, this promising drug will provide US oncologists with an important new immunotherapy option for the treatment of CSCC,” she added. 

 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the immune checkpoint inhibitor cosibelimab (Unloxcyt; Checkpoint Therapeutics) for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. 

The programmed death ligand-1 (PD-L1)–blocking antibody is the first and only treatment of its kind approved for advanced CSCC, according to a Checkpoint Therapeutics press release. The FDA approval was based on findings from the multicenter, open-label Study CK-301-101 trial of 109 patients. 

In that trial, the objective response rate (ORR) was 47% in 78 patients with metastatic CSCC and 48% in 31 patients with locally advanced CSCC. Median duration of response (DOR) in treated patients was not reached in those with metastatic disease and was 17.7 months in those with locally advanced disease, according to the FDA approval notice.

Adverse reactions occurring in at least 10% of patients included fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.

The recommended treatment dose, according to the prescribing information, is 1200 mg given as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.

The agent offers “a differentiated treatment option versus available therapies by binding to PD-L1, rather than programmed death receptor-1 (PD-1), to release the inhibitory effects of PD-L1 on the anti-tumor immune response,” Checkpoint Therapeutics president and chief executive officer James Oliviero stated in the company press release. 

The agent has also “demonstrated the ability to induce antibody-dependent cell-mediated cytotoxicity, another potential differentiating feature of the drug compared to existing marketing therapies for CSCC,” Oliviero noted.

“CSCC is the second most common form of skin cancer, and those diagnosed with advanced disease that has recurred or metastasized face a poor prognosis,” stated Emily Ruiz, MD, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital and director of the High-Risk Skin Cancer Clinic at Dana-Farber Brigham Cancer Center. 

“With its dual mechanisms of action and compelling safety profile, this promising drug will provide US oncologists with an important new immunotherapy option for the treatment of CSCC,” she added. 

 

A version of this article appeared on Medscape.com.

SAN ANTONIO — For patients with so-called “good-risk” ductal carcinoma in situ (DCIS) who did not have radiation therapy after breast-conserving surgery, adjuvant tamoxifen reduced their overall risks for invasive recurrence, but not their risks for recurrence in either the same or contralateral breast.

These findings come from an exploratory analysis of combined data from two clinical trials. They suggest that, for this select group of patients, the choice to forgo radiation following definitive surgery may be an acceptable option, assuming that they follow a full course of endocrine therapy.

“In the absence of survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared decision process, and I think that this data helps us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk [ductal carcinoma in situ],” said Jean L. Wright, MD, from the University of North Carolina at Chapel Hill.

She presented the findings in an oral abstract session and media briefing at San Antonio Breast Cancer Symposium (SABCS) 2024.

 

Trial Results Combined

Wright and colleagues looked at pooled data from two clinical trials that enrolled patients with low- or intermediate-grade DCIS with tumor size no larger than 2.5 cm, grade 1 or 2 lesions, and with surgical margins ≥ 3 mm.

The trials included NRG/RTOG 9804, with 317 patients who fit the “good-risk category,” and ECOG-ACRIN E5194, which included a cohort of 561 patients that met the good-risk definition used for the exploratory analysis.

In each trial, tamoxifen use was optional, and choices were tracked. In the NRG/RTOG trial, 66% of patients used tamoxifen and 34% did not. The respective percentages in the ECOG/ACRIN trial were 30% and 70%.

The majority of patients were adherent to the 5-year prescribed course of tamoxifen, Wright said.

 

Analysis Details

In the combined data, the median age of patients who used tamoxifen vs who did not use tamoxifen was 58 vs 61 years.

In all, 23% of women in both the tamoxifen yes or no groups were premenopausal, with the remainder either postmenopausal or of unknown menopausal status.

After a median follow-up of 14.85 years, the rate of 15-year ipsilateral breast recurrence (IBR) was 19% for patients who did not receive tamoxifen vs 11.4% for those who did. This translated into a hazard ratio for IBR on tamoxifen of 0.52 (P = .001).

Tamoxifen also reduced the risk for invasive recurrence in the same breast, with a 15-year invasive IBR rate of 11.5% in the no tamoxifen group vs 6% in the yes tamoxifen group.

However, as noted before, tamoxifen use was not associated with significant reduction in the risk for noninvasive DCIS recurrence in the same breast, as evidenced by a 15-year DCIS IBR rate of 8.1% without tamoxifen and 5.5% with tamoxifen, a difference that did not reach statistical significance.

 

A Surprising Result

One finding from the data that seemed to defy clinical wisdom was that tamoxifen use did not appear to significantly reduce the risk for events in the other breast. The 15-year rate of contralateral breast events was 8.8% in the no-tamoxifen group vs 5.6% in the yes tamoxifen group, a difference that was not statically significant.

“It was surprising that there was so little effect on contralateral disease,” commented Elinor Sawyer, MBBS, PhD, the invited discussant.

“But I think it’s really important, this decrease in ipsilateral invasive recurrence [with tamoxifen] because there are studies such as the Sloane study from the United Kingdom that show that if you develop an invasive recurrence after DCIS, you have a worse survival than those who develop a pure DCIS recurrence,” she said.

At the media briefing held prior to Wright’s presentation, moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio in Texas, also said that she found it surprising that tamoxifen did not reduce risk for contralateral breast cancer “since every study that we’ve done has shown that.”

“I also found that result a little bit surprising,” Wright agreed.

“I think the main feature that we want to focus on is that this was a group of patients with a very clear inclusion criteria of this good-risk DCIS, and even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So I’m wondering if it’s perhaps that it’s related to the fact that patients that were enrolled in these studies had really low-risk features and perhaps just had a lower risk of contralateral breast events as compared to a broader population of patients with DCIS,” she said.

The analysis by Wright and colleagues was supported by grants from the National Cancer Institute. Wright reported receiving honoraria from ASTRO and PER. Sawyer disclosed receiving grants/research support from Pfizer, Seagen, and IQIVIA. Kaklamani disclosed serving as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead, Lilly, Menarini, and Novartis and receiving research support from Eisai.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — For patients with so-called “good-risk” ductal carcinoma in situ (DCIS) who did not have radiation therapy after breast-conserving surgery, adjuvant tamoxifen reduced their overall risks for invasive recurrence, but not their risks for recurrence in either the same or contralateral breast.

These findings come from an exploratory analysis of combined data from two clinical trials. They suggest that, for this select group of patients, the choice to forgo radiation following definitive surgery may be an acceptable option, assuming that they follow a full course of endocrine therapy.

“In the absence of survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared decision process, and I think that this data helps us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk [ductal carcinoma in situ],” said Jean L. Wright, MD, from the University of North Carolina at Chapel Hill.

She presented the findings in an oral abstract session and media briefing at San Antonio Breast Cancer Symposium (SABCS) 2024.

 

Trial Results Combined

Wright and colleagues looked at pooled data from two clinical trials that enrolled patients with low- or intermediate-grade DCIS with tumor size no larger than 2.5 cm, grade 1 or 2 lesions, and with surgical margins ≥ 3 mm.

The trials included NRG/RTOG 9804, with 317 patients who fit the “good-risk category,” and ECOG-ACRIN E5194, which included a cohort of 561 patients that met the good-risk definition used for the exploratory analysis.

In each trial, tamoxifen use was optional, and choices were tracked. In the NRG/RTOG trial, 66% of patients used tamoxifen and 34% did not. The respective percentages in the ECOG/ACRIN trial were 30% and 70%.

The majority of patients were adherent to the 5-year prescribed course of tamoxifen, Wright said.

 

Analysis Details

In the combined data, the median age of patients who used tamoxifen vs who did not use tamoxifen was 58 vs 61 years.

In all, 23% of women in both the tamoxifen yes or no groups were premenopausal, with the remainder either postmenopausal or of unknown menopausal status.

After a median follow-up of 14.85 years, the rate of 15-year ipsilateral breast recurrence (IBR) was 19% for patients who did not receive tamoxifen vs 11.4% for those who did. This translated into a hazard ratio for IBR on tamoxifen of 0.52 (P = .001).

Tamoxifen also reduced the risk for invasive recurrence in the same breast, with a 15-year invasive IBR rate of 11.5% in the no tamoxifen group vs 6% in the yes tamoxifen group.

However, as noted before, tamoxifen use was not associated with significant reduction in the risk for noninvasive DCIS recurrence in the same breast, as evidenced by a 15-year DCIS IBR rate of 8.1% without tamoxifen and 5.5% with tamoxifen, a difference that did not reach statistical significance.

 

A Surprising Result

One finding from the data that seemed to defy clinical wisdom was that tamoxifen use did not appear to significantly reduce the risk for events in the other breast. The 15-year rate of contralateral breast events was 8.8% in the no-tamoxifen group vs 5.6% in the yes tamoxifen group, a difference that was not statically significant.

“It was surprising that there was so little effect on contralateral disease,” commented Elinor Sawyer, MBBS, PhD, the invited discussant.

“But I think it’s really important, this decrease in ipsilateral invasive recurrence [with tamoxifen] because there are studies such as the Sloane study from the United Kingdom that show that if you develop an invasive recurrence after DCIS, you have a worse survival than those who develop a pure DCIS recurrence,” she said.

At the media briefing held prior to Wright’s presentation, moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio in Texas, also said that she found it surprising that tamoxifen did not reduce risk for contralateral breast cancer “since every study that we’ve done has shown that.”

“I also found that result a little bit surprising,” Wright agreed.

“I think the main feature that we want to focus on is that this was a group of patients with a very clear inclusion criteria of this good-risk DCIS, and even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So I’m wondering if it’s perhaps that it’s related to the fact that patients that were enrolled in these studies had really low-risk features and perhaps just had a lower risk of contralateral breast events as compared to a broader population of patients with DCIS,” she said.

The analysis by Wright and colleagues was supported by grants from the National Cancer Institute. Wright reported receiving honoraria from ASTRO and PER. Sawyer disclosed receiving grants/research support from Pfizer, Seagen, and IQIVIA. Kaklamani disclosed serving as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead, Lilly, Menarini, and Novartis and receiving research support from Eisai.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — For patients with so-called “good-risk” ductal carcinoma in situ (DCIS) who did not have radiation therapy after breast-conserving surgery, adjuvant tamoxifen reduced their overall risks for invasive recurrence, but not their risks for recurrence in either the same or contralateral breast.

These findings come from an exploratory analysis of combined data from two clinical trials. They suggest that, for this select group of patients, the choice to forgo radiation following definitive surgery may be an acceptable option, assuming that they follow a full course of endocrine therapy.

“In the absence of survival impact for adjuvant therapy, the decision to recommend radiation therapy or endocrine therapy should be part of a shared decision process, and I think that this data helps us provide clearer data points to our patients to help them make choices between endocrine therapy and radiation therapy in the setting of good-risk [ductal carcinoma in situ],” said Jean L. Wright, MD, from the University of North Carolina at Chapel Hill.

She presented the findings in an oral abstract session and media briefing at San Antonio Breast Cancer Symposium (SABCS) 2024.

 

Trial Results Combined

Wright and colleagues looked at pooled data from two clinical trials that enrolled patients with low- or intermediate-grade DCIS with tumor size no larger than 2.5 cm, grade 1 or 2 lesions, and with surgical margins ≥ 3 mm.

The trials included NRG/RTOG 9804, with 317 patients who fit the “good-risk category,” and ECOG-ACRIN E5194, which included a cohort of 561 patients that met the good-risk definition used for the exploratory analysis.

In each trial, tamoxifen use was optional, and choices were tracked. In the NRG/RTOG trial, 66% of patients used tamoxifen and 34% did not. The respective percentages in the ECOG/ACRIN trial were 30% and 70%.

The majority of patients were adherent to the 5-year prescribed course of tamoxifen, Wright said.

 

Analysis Details

In the combined data, the median age of patients who used tamoxifen vs who did not use tamoxifen was 58 vs 61 years.

In all, 23% of women in both the tamoxifen yes or no groups were premenopausal, with the remainder either postmenopausal or of unknown menopausal status.

After a median follow-up of 14.85 years, the rate of 15-year ipsilateral breast recurrence (IBR) was 19% for patients who did not receive tamoxifen vs 11.4% for those who did. This translated into a hazard ratio for IBR on tamoxifen of 0.52 (P = .001).

Tamoxifen also reduced the risk for invasive recurrence in the same breast, with a 15-year invasive IBR rate of 11.5% in the no tamoxifen group vs 6% in the yes tamoxifen group.

However, as noted before, tamoxifen use was not associated with significant reduction in the risk for noninvasive DCIS recurrence in the same breast, as evidenced by a 15-year DCIS IBR rate of 8.1% without tamoxifen and 5.5% with tamoxifen, a difference that did not reach statistical significance.

 

A Surprising Result

One finding from the data that seemed to defy clinical wisdom was that tamoxifen use did not appear to significantly reduce the risk for events in the other breast. The 15-year rate of contralateral breast events was 8.8% in the no-tamoxifen group vs 5.6% in the yes tamoxifen group, a difference that was not statically significant.

“It was surprising that there was so little effect on contralateral disease,” commented Elinor Sawyer, MBBS, PhD, the invited discussant.

“But I think it’s really important, this decrease in ipsilateral invasive recurrence [with tamoxifen] because there are studies such as the Sloane study from the United Kingdom that show that if you develop an invasive recurrence after DCIS, you have a worse survival than those who develop a pure DCIS recurrence,” she said.

At the media briefing held prior to Wright’s presentation, moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio in Texas, also said that she found it surprising that tamoxifen did not reduce risk for contralateral breast cancer “since every study that we’ve done has shown that.”

“I also found that result a little bit surprising,” Wright agreed.

“I think the main feature that we want to focus on is that this was a group of patients with a very clear inclusion criteria of this good-risk DCIS, and even though the definition of good-risk DCIS included patients with [tumors] up to 2.5 cm in DCIS, we saw that, in reality, the patients enrolled had very small DCIS. So I’m wondering if it’s perhaps that it’s related to the fact that patients that were enrolled in these studies had really low-risk features and perhaps just had a lower risk of contralateral breast events as compared to a broader population of patients with DCIS,” she said.

The analysis by Wright and colleagues was supported by grants from the National Cancer Institute. Wright reported receiving honoraria from ASTRO and PER. Sawyer disclosed receiving grants/research support from Pfizer, Seagen, and IQIVIA. Kaklamani disclosed serving as a speaker and/or consultant for AstraZeneca, Celldex Therapeutics, Daiichi Sankyo, Genentech, Gilead, Lilly, Menarini, and Novartis and receiving research support from Eisai.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — Second-line treatment with imlunestrant improved progression-free survival compared with standard endocrine monotherapy in patients with advanced estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who had ESR1 mutations, according to recent findings from the EMBER-3 trial.

This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.

Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”

The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.

However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.

First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.

Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.

The oral SERD imlunestrant is one such candidate.

The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.

About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.

Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.

When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.

Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.

The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).

Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.

All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.

The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.

EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.

A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.

Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.

She was also concerned about the use of monotherapy in the standard care arm.

“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.

Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.

Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Second-line treatment with imlunestrant improved progression-free survival compared with standard endocrine monotherapy in patients with advanced estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who had ESR1 mutations, according to recent findings from the EMBER-3 trial.

This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.

Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”

The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.

However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.

First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.

Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.

The oral SERD imlunestrant is one such candidate.

The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.

About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.

Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.

When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.

Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.

The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).

Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.

All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.

The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.

EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.

A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.

Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.

She was also concerned about the use of monotherapy in the standard care arm.

“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.

Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.

Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Second-line treatment with imlunestrant improved progression-free survival compared with standard endocrine monotherapy in patients with advanced estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who had ESR1 mutations, according to recent findings from the EMBER-3 trial.

This progression-free survival benefit with imlunestrant did not extend to the overall population, but a combination of imlunestrant plus abemaciclib did lead to a significant improvement in progression-free survival compared with imlunestrant alone, regardless of patients’ ESR1 mutation status.

Lead author Komal Jhaveri, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York City, called the findings “encouraging.”

The phase 3 results raise the possibility of a second-line all-oral targeted therapy option for patients with ER–positive, HER2–negative advanced breast cancer, said Jhaveri, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, which were published simultaneously in The New England Journal of Medicine.

However, outside experts provided a note of caution that the trial design may limit how relevant the findings are to clinical practice.

First-line treatment for advanced ER–positive, HER2–negative breast cancer includes an aromatase inhibitor, such as exemestane, and a CDK4/6 inhibitor, such as abemaciclib. However, an ESR1 mutation may develop, which can undermine the effectiveness of the aromatase inhibitor. These patients may swap in a selective estrogen receptor degrader (SERD) — typically, the injectable fulvestrant — in place of the aromatase inhibitor.

Over the past several years, researchers have searched for a better agent than fulvestrant because this injectable drug has limited efficacy in patients with ESR1 mutations, and the monthly intramuscular shots are painful and inconvenient for patients.

The oral SERD imlunestrant is one such candidate.

The EMBER-3 trial initially randomized 661 patients after progression/recurrence evenly to either imlunestrant monotherapy (400 mg once daily) or a standard treatment arm that included either exemestane or fulvestrant, with 90% of these patients receiving fulvestrant. Investigators added a third combination arm shortly after the trial started, which included 213 patients who received imlunestrant plus abemaciclib.

About 60% of the overall population had received prior CDK4/6 inhibitors, primarily palbociclib and ribociclib. About 37% of the study population had ESR1 mutations.

Among patients with ESR1 mutations, imlunestrant monotherapy led to a significant improvement in median progression-free survival of 5.5 months vs 3.8 months in the standard care arm (P < .001). Among all patients, however, progression-free survival was no different between the two arms — 5.6 months in the imlunestrant group vs 5.5 months in the standard care group.

When comparing the two treatment arms in the overall population, the median progression-free survival was significantly better in patients who received imlunestrant plus abemaciclib — 9.4 months vs 5.5 months in the imlunestrant group (hazard ratio [HR] for progression or death, 0.57; P < .001). The progression-free survival benefit held across most patient subgroups, regardless of ESR1 mutation status, as well as among patients who had received a CDK4/6 inhibitor previously.

Data from other studies presented at SABCS indicate that another SERD, elacestrant, in combination with abemaciclib, may provide a similar progression-free survival benefit in this patient population. Elacestrant was approved by the US Food and Drug Administration (FDA) in January 2023 for second-line treatment of patients with advanced breast cancer and ESR1 mutations.

The EMBER trial also reported early overall survival findings. Although immature, overall survival trends favored imlunestrant over the standard treatment. The estimated overall survival at 18 months was 77% in the imlunestrant group and 58.6% in the standard therapy group among patients with ESR1 mutations (HR, 0.55), and 78.6% in the imlunestrant group vs 71.8% in the standard-therapy group for all patients (HR, 0.69).

Common all-grade adverse events with imlunestrant vs standard therapy included fatigue (22.6% vs 13.3%), diarrhea (21.4% vs 11.7%), and nausea (17% vs 13%). Grade 3 or higher anemia and neutropenia were low and similar in both arms.

All-grade diarrhea (86%) and nausea (49%) were more common with the combination of imlunestrant and abemaciclib.

The incidence of grade 3 or higher events was 17% with imlunestrant monotherapy, 21% for standard treatment, and 49% for imlunestrant plus abemaciclib.

EMBER-3 discussant Harold Burstein, MD, PhD, a breast oncologist at the Dana-Farber Cancer Institute, Boston, said that, overall, oral SERDs are starting to “break out from the ESR1 mutation box,” perhaps reflecting the idea that an agent more active than fulvestrant in combination with a non-cross–resistant CDK4/6 inhibitor like abemaciclib might lead to a better long-term outcome, regardless of ESR1 status.

A major limit of EMBER-3, however, is that it did not compare imlunestrant/abemaciclib with fulvestrant/abemaciclib, which would have been a true standard-of-care control, said Burstein.

Kathy Miller, MD, a breast oncologist at Indiana University, Indianapolis, agreed.

She was also concerned about the use of monotherapy in the standard care arm.

“Monotherapy hormone therapy is not what people would be treated with,” Miller said. Patients would typically get fulvestrant with either a targeted therapy or everolimus.

Without appropriate controls, “the data are impossible to interpret” in the context of current practice, Miller told Medscape Medical News.

Eli Lilly, maker of imlunestrant, funded, designed, and largely conducted the trial. Jhaveri is a consultant and researcher for the company. Burstein and Miller had no disclosures. Miller is an editorial advisor for Medscape Oncology.
 

A version of this article appeared on Medscape.com.

Treated with a dexamethasone-sparing regimen, frail older adult patients with newly diagnosed multiple myeloma (MM) show significant reductions in disease progression and improvements in quality of life, new research shows.

The study “is the first randomized phase 3 study dedicated to frail patients,” said first author Salomon Manier, MD, PhD, an associate professor of hematology at Lille University Hospital, Lille, France. He presented the findings this week at the American Society of Hematology (ASH) 2024 Annual Meeting in San Diego.

“It shows that daratumumab-lenalidomide [with limited dexamethasone] led to a significant reduced risk of progression or death by 49% in frail patients, with a favorable safety profile and an improved health-related quality of life,” Manier said.

Older adult patients who are newly diagnosed with MM have varying levels of fitness or frailty and have been shown to have shorter survival, with higher rates of nonhematologic adverse events and treatment discontinuation.

While the regimen of daratumumab, lenalidomide, and dexamethasone has become a standard of care, with efficacy and tolerance, including for patients with frailty, the infection and pneumonia rates with the approach can be high, particularly for patients with frailty.

To evaluate if an alternative, dexamethasone-sparing approach could improve outcomes while limiting toxicity for older adults, Manier and his colleagues conducted the prospective, open-label phase 3 IFM2017-03 trial, involving 295 patients (age, 65 years) with newly diagnosed MM at 90 centers in France.

The patients had a median age of 81, with 84% older than 75 years and 61% older than 80 years. All had an Eastern Cooperative Oncology Group proxy frailty score ≥ 2.

The patients were randomized 1:2 to treatment either with the Rd regimen of 28-day cycles of lenalidomide (25 mg/d, 21/28) and dexamethasone (20 mg once weekly) or with the dexamethasone-sparing regimen (DR) of daratumumab (1800 mg subcutaneous once weekly for 8 weeks, once every 2 weeks for 16 weeks, and once every 4 weeks thereafter), lenalidomide (25 mg/d, 21/28), and two cycles of dexamethasone (20 mg once weekly for 8 weeks then stopping).

The randomization included stratification based on age and cancer stage. Baseline characteristics were well balanced in the two groups.

Both regimens were administered until disease progression or unacceptable toxicity.

As of the data cut-off in November 2024, with a median follow-up of 46.3 months, 81 of the original 200 patients in the DR arm remained on treatment, and 11 of 95 continued in the Rd arm.

The overall median treatment duration among the 200 original patients in the DR arm was 31.6 months and 14.3 months in the Rd arm.

The study met its primary endpoint of progression-free survival (PFS), with a median rate of 53.4 months in the DR arm vs 22.5 months in the Rd arm (hazard ratio [HR], 0.51; P < .0001).

The improved PFS in the DR arm was observed across all subgroups based on age, Charlson comorbidity index, cancer stage, cytogenetics, and creatinine clearance; however, those with lower frailty scores had better outcomes in both groups.

A median overall survival was not reached in the DR arm vs 47.2 months in the Rd arm (HR, 0.52; P = .0001).

The DR arm also showed a higher overall best response rate of 94% vs 86% (P = .005), respectively, with deeper responses in the DR arm at all time points, including the earliest points at 4 months.

In terms of adverse events (AEs), at least one AE of grade ≥ 3 occurred in 89% in the DR arm and 79% in the Rd arm.

Those in the DR arm had significantly more grade 3 or higher hematologic AEs with neutropenia (62% vs 34%); however, grade ≥ 3 infections were similar, with 19% in the DR arm and 21% in the Rd arm. Infections involving pneumonia occurred in 6% and 8%, respectively.

There were no significant differences between the two arms in discontinuations due to AEs (30% in the DR arm and 34% in the Rd arm).

While health-related quality of life measures at baseline were well balanced between the two groups, those in the DR arm reported significantly shorter times to clinically meaningful improvement in all domains of the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30).

“The safety profile was significantly improved and was favorable, without increased infection or pneumonia rates, with similar rates of treatment discontinuation,” Manier said.

Based on the findings, “we believe that the dexamethasone-sparing strategy is effective and safe for treating these frail patients with multiple myeloma,” he added.

Commenting on the study, Manni Mohyuddin, MD, an assistant professor in the multiple myeloma program at the Huntsman Cancer Institute, University of Utah, Salt Lake City, noted that, with the popularity of triplet regimens such as daratumumab, lenalidomide, and dexamethasone, the Rd regimen in the study is not as commonly used.

“But what this trial tells us is that efficacy outcomes in such a group of patients are encouraging despite getting rid of dexamethasone so quickly,” he said in an interview.

However, “while the tide is changing, dexamethasone is still given long-term, week after week after week in most myeloma protocols and in the community,” he noted. “Hopefully, this trial, and some of the other work, will lead to a change in this space.” 

Mohyuddin suggests one approach can involve starting off with just daratumumab and a low dose of dexamethasone, then adding lenalidomide at a lower dose later in a sequential/graded approach.

“Other approaches that should be studied should be bispecific antibodies used sparingly, with less frequent dosing, or finite period,” he added. “There is lot to refine.”

Mohyuddin added a critique that the study’s endpoint of PFS may not have been ideal for the population of elderly and frail patients.

“Older people generally prioritize functional independence and quality of life, and perhaps a more patient-centered endpoint could have led to an even more informative study,” he said.

Manier’s disclosures included consultancy with Takeda Pharmaceuticals, Sanofi, Novartis, Janssen, GlaxoSmithKline, Celgene/BMS, Amgen, Adaptive Biotechnologies, Roche, Regeneron, and AbbVie. Mohyuddin had no disclosures.

A version of this article appeared on Medscape.com.

Treated with a dexamethasone-sparing regimen, frail older adult patients with newly diagnosed multiple myeloma (MM) show significant reductions in disease progression and improvements in quality of life, new research shows.

The study “is the first randomized phase 3 study dedicated to frail patients,” said first author Salomon Manier, MD, PhD, an associate professor of hematology at Lille University Hospital, Lille, France. He presented the findings this week at the American Society of Hematology (ASH) 2024 Annual Meeting in San Diego.

“It shows that daratumumab-lenalidomide [with limited dexamethasone] led to a significant reduced risk of progression or death by 49% in frail patients, with a favorable safety profile and an improved health-related quality of life,” Manier said.

Older adult patients who are newly diagnosed with MM have varying levels of fitness or frailty and have been shown to have shorter survival, with higher rates of nonhematologic adverse events and treatment discontinuation.

While the regimen of daratumumab, lenalidomide, and dexamethasone has become a standard of care, with efficacy and tolerance, including for patients with frailty, the infection and pneumonia rates with the approach can be high, particularly for patients with frailty.

To evaluate if an alternative, dexamethasone-sparing approach could improve outcomes while limiting toxicity for older adults, Manier and his colleagues conducted the prospective, open-label phase 3 IFM2017-03 trial, involving 295 patients (age, 65 years) with newly diagnosed MM at 90 centers in France.

The patients had a median age of 81, with 84% older than 75 years and 61% older than 80 years. All had an Eastern Cooperative Oncology Group proxy frailty score ≥ 2.

The patients were randomized 1:2 to treatment either with the Rd regimen of 28-day cycles of lenalidomide (25 mg/d, 21/28) and dexamethasone (20 mg once weekly) or with the dexamethasone-sparing regimen (DR) of daratumumab (1800 mg subcutaneous once weekly for 8 weeks, once every 2 weeks for 16 weeks, and once every 4 weeks thereafter), lenalidomide (25 mg/d, 21/28), and two cycles of dexamethasone (20 mg once weekly for 8 weeks then stopping).

The randomization included stratification based on age and cancer stage. Baseline characteristics were well balanced in the two groups.

Both regimens were administered until disease progression or unacceptable toxicity.

As of the data cut-off in November 2024, with a median follow-up of 46.3 months, 81 of the original 200 patients in the DR arm remained on treatment, and 11 of 95 continued in the Rd arm.

The overall median treatment duration among the 200 original patients in the DR arm was 31.6 months and 14.3 months in the Rd arm.

The study met its primary endpoint of progression-free survival (PFS), with a median rate of 53.4 months in the DR arm vs 22.5 months in the Rd arm (hazard ratio [HR], 0.51; P < .0001).

The improved PFS in the DR arm was observed across all subgroups based on age, Charlson comorbidity index, cancer stage, cytogenetics, and creatinine clearance; however, those with lower frailty scores had better outcomes in both groups.

A median overall survival was not reached in the DR arm vs 47.2 months in the Rd arm (HR, 0.52; P = .0001).

The DR arm also showed a higher overall best response rate of 94% vs 86% (P = .005), respectively, with deeper responses in the DR arm at all time points, including the earliest points at 4 months.

In terms of adverse events (AEs), at least one AE of grade ≥ 3 occurred in 89% in the DR arm and 79% in the Rd arm.

Those in the DR arm had significantly more grade 3 or higher hematologic AEs with neutropenia (62% vs 34%); however, grade ≥ 3 infections were similar, with 19% in the DR arm and 21% in the Rd arm. Infections involving pneumonia occurred in 6% and 8%, respectively.

There were no significant differences between the two arms in discontinuations due to AEs (30% in the DR arm and 34% in the Rd arm).

While health-related quality of life measures at baseline were well balanced between the two groups, those in the DR arm reported significantly shorter times to clinically meaningful improvement in all domains of the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30).

“The safety profile was significantly improved and was favorable, without increased infection or pneumonia rates, with similar rates of treatment discontinuation,” Manier said.

Based on the findings, “we believe that the dexamethasone-sparing strategy is effective and safe for treating these frail patients with multiple myeloma,” he added.

Commenting on the study, Manni Mohyuddin, MD, an assistant professor in the multiple myeloma program at the Huntsman Cancer Institute, University of Utah, Salt Lake City, noted that, with the popularity of triplet regimens such as daratumumab, lenalidomide, and dexamethasone, the Rd regimen in the study is not as commonly used.

“But what this trial tells us is that efficacy outcomes in such a group of patients are encouraging despite getting rid of dexamethasone so quickly,” he said in an interview.

However, “while the tide is changing, dexamethasone is still given long-term, week after week after week in most myeloma protocols and in the community,” he noted. “Hopefully, this trial, and some of the other work, will lead to a change in this space.” 

Mohyuddin suggests one approach can involve starting off with just daratumumab and a low dose of dexamethasone, then adding lenalidomide at a lower dose later in a sequential/graded approach.

“Other approaches that should be studied should be bispecific antibodies used sparingly, with less frequent dosing, or finite period,” he added. “There is lot to refine.”

Mohyuddin added a critique that the study’s endpoint of PFS may not have been ideal for the population of elderly and frail patients.

“Older people generally prioritize functional independence and quality of life, and perhaps a more patient-centered endpoint could have led to an even more informative study,” he said.

Manier’s disclosures included consultancy with Takeda Pharmaceuticals, Sanofi, Novartis, Janssen, GlaxoSmithKline, Celgene/BMS, Amgen, Adaptive Biotechnologies, Roche, Regeneron, and AbbVie. Mohyuddin had no disclosures.

A version of this article appeared on Medscape.com.

Treated with a dexamethasone-sparing regimen, frail older adult patients with newly diagnosed multiple myeloma (MM) show significant reductions in disease progression and improvements in quality of life, new research shows.

The study “is the first randomized phase 3 study dedicated to frail patients,” said first author Salomon Manier, MD, PhD, an associate professor of hematology at Lille University Hospital, Lille, France. He presented the findings this week at the American Society of Hematology (ASH) 2024 Annual Meeting in San Diego.

“It shows that daratumumab-lenalidomide [with limited dexamethasone] led to a significant reduced risk of progression or death by 49% in frail patients, with a favorable safety profile and an improved health-related quality of life,” Manier said.

Older adult patients who are newly diagnosed with MM have varying levels of fitness or frailty and have been shown to have shorter survival, with higher rates of nonhematologic adverse events and treatment discontinuation.

While the regimen of daratumumab, lenalidomide, and dexamethasone has become a standard of care, with efficacy and tolerance, including for patients with frailty, the infection and pneumonia rates with the approach can be high, particularly for patients with frailty.

To evaluate if an alternative, dexamethasone-sparing approach could improve outcomes while limiting toxicity for older adults, Manier and his colleagues conducted the prospective, open-label phase 3 IFM2017-03 trial, involving 295 patients (age, 65 years) with newly diagnosed MM at 90 centers in France.

The patients had a median age of 81, with 84% older than 75 years and 61% older than 80 years. All had an Eastern Cooperative Oncology Group proxy frailty score ≥ 2.

The patients were randomized 1:2 to treatment either with the Rd regimen of 28-day cycles of lenalidomide (25 mg/d, 21/28) and dexamethasone (20 mg once weekly) or with the dexamethasone-sparing regimen (DR) of daratumumab (1800 mg subcutaneous once weekly for 8 weeks, once every 2 weeks for 16 weeks, and once every 4 weeks thereafter), lenalidomide (25 mg/d, 21/28), and two cycles of dexamethasone (20 mg once weekly for 8 weeks then stopping).

The randomization included stratification based on age and cancer stage. Baseline characteristics were well balanced in the two groups.

Both regimens were administered until disease progression or unacceptable toxicity.

As of the data cut-off in November 2024, with a median follow-up of 46.3 months, 81 of the original 200 patients in the DR arm remained on treatment, and 11 of 95 continued in the Rd arm.

The overall median treatment duration among the 200 original patients in the DR arm was 31.6 months and 14.3 months in the Rd arm.

The study met its primary endpoint of progression-free survival (PFS), with a median rate of 53.4 months in the DR arm vs 22.5 months in the Rd arm (hazard ratio [HR], 0.51; P < .0001).

The improved PFS in the DR arm was observed across all subgroups based on age, Charlson comorbidity index, cancer stage, cytogenetics, and creatinine clearance; however, those with lower frailty scores had better outcomes in both groups.

A median overall survival was not reached in the DR arm vs 47.2 months in the Rd arm (HR, 0.52; P = .0001).

The DR arm also showed a higher overall best response rate of 94% vs 86% (P = .005), respectively, with deeper responses in the DR arm at all time points, including the earliest points at 4 months.

In terms of adverse events (AEs), at least one AE of grade ≥ 3 occurred in 89% in the DR arm and 79% in the Rd arm.

Those in the DR arm had significantly more grade 3 or higher hematologic AEs with neutropenia (62% vs 34%); however, grade ≥ 3 infections were similar, with 19% in the DR arm and 21% in the Rd arm. Infections involving pneumonia occurred in 6% and 8%, respectively.

There were no significant differences between the two arms in discontinuations due to AEs (30% in the DR arm and 34% in the Rd arm).

While health-related quality of life measures at baseline were well balanced between the two groups, those in the DR arm reported significantly shorter times to clinically meaningful improvement in all domains of the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30).

“The safety profile was significantly improved and was favorable, without increased infection or pneumonia rates, with similar rates of treatment discontinuation,” Manier said.

Based on the findings, “we believe that the dexamethasone-sparing strategy is effective and safe for treating these frail patients with multiple myeloma,” he added.

Commenting on the study, Manni Mohyuddin, MD, an assistant professor in the multiple myeloma program at the Huntsman Cancer Institute, University of Utah, Salt Lake City, noted that, with the popularity of triplet regimens such as daratumumab, lenalidomide, and dexamethasone, the Rd regimen in the study is not as commonly used.

“But what this trial tells us is that efficacy outcomes in such a group of patients are encouraging despite getting rid of dexamethasone so quickly,” he said in an interview.

However, “while the tide is changing, dexamethasone is still given long-term, week after week after week in most myeloma protocols and in the community,” he noted. “Hopefully, this trial, and some of the other work, will lead to a change in this space.” 

Mohyuddin suggests one approach can involve starting off with just daratumumab and a low dose of dexamethasone, then adding lenalidomide at a lower dose later in a sequential/graded approach.

“Other approaches that should be studied should be bispecific antibodies used sparingly, with less frequent dosing, or finite period,” he added. “There is lot to refine.”

Mohyuddin added a critique that the study’s endpoint of PFS may not have been ideal for the population of elderly and frail patients.

“Older people generally prioritize functional independence and quality of life, and perhaps a more patient-centered endpoint could have led to an even more informative study,” he said.

Manier’s disclosures included consultancy with Takeda Pharmaceuticals, Sanofi, Novartis, Janssen, GlaxoSmithKline, Celgene/BMS, Amgen, Adaptive Biotechnologies, Roche, Regeneron, and AbbVie. Mohyuddin had no disclosures.

A version of this article appeared on Medscape.com.

Patients with BRCA mutations and a history of early-onset breast cancer benefited from risk-reducing surgeries, according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.

Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.

“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”

“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing. 

Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.

The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery. 

Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.

During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported. 

The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not. 

During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).

For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.

“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.

Overall survival results were similar in patients who underwent one or both surgeries.

Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”

In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.

The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.

In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?” 

This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said. 

“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.

The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Patients with BRCA mutations and a history of early-onset breast cancer benefited from risk-reducing surgeries, according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.

Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.

“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”

“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing. 

Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.

The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery. 

Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.

During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported. 

The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not. 

During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).

For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.

“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.

Overall survival results were similar in patients who underwent one or both surgeries.

Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”

In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.

The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.

In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?” 

This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said. 

“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.

The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.

A version of this article first appeared on Medscape.com.

Patients with BRCA mutations and a history of early-onset breast cancer benefited from risk-reducing surgeries, according to new data presented at the San Antonio Breast Cancer Symposium (SABCS) 2024.

Having a risk-reducing mastectomy or salpingo-oophorectomy was associated with significantly improved overall survival and disease-free survival in BRCA-mutation carriers who had been diagnosed with a first breast cancer at age ≤ 40 years.

“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA-mutation carriers with a prior history of early-onset breast cancer,” study investigator Matteo Lambertini, MD, PhD, oncologist with the University of Genova–IRCCS Policlinico San Martino Hospital in Genoa, Italy, said in a statement from the SABCS, where he presented the findings. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so that the risks and benefits of these procedures can be carefully weighed.”

“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with young-onset of breast cancer below the age of 40 years,” Lambertini added during a press briefing. 

Various risk-reducing strategies, including risk-reducing surgeries, are recommended for BRCA-mutation carriers without a prior history of cancer, but the impact of these surgeries among younger populations with a history of early-onset breast cancer has been less clear.

The new findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5290 patients with likely pathogenic/pathogenic germline BRCA1 and/or BRCA2 mutations who were diagnosed with stages I-III breast cancer at ≤ 40 years. The risk-reducing mastectomy analysis included 2910 patients (55%) who underwent the surgery less than 1 year from diagnosis and 2380 who opted not to have the surgery. 

Primary endpoint was overall survival, and disease-free survival and breast cancer-free interval were secondary endpoints. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies.

During median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of dying (adjusted hazard ratio [aHR], 0.65) as well as a significant improvement in both disease-free survival (aHR, 0.58) and breast cancer-free interval (aHR, 0.55). The improved outcomes were seen in both BRCA1 and BRCA2 carriers, Lambertini reported. 

The risk-reducing salpingo-oophorectomy analysis included 2782 patients who underwent this surgery a median of 3 years from diagnosis and 2508 who did not. 

During median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death (aHR, 0.58) as well as an improvement in both disease-free survival (aHR, 0.68) and breast cancer-free interval (aHR, 0.65).

For risk-reducing salpingo-oophorectomy, there was an interaction based on breast cancer subtype and BRCA mutation.

“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative disease, as compared to those with BRCA2 pathogenic variants or luminal disease,” Lambertini reported.

Overall survival results were similar in patients who underwent one or both surgeries.

Briefing moderator Kate Lathrop, MD, with the University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. Having datasets like this helps us give patients “potentially our best estimate of the amount of reduction of risk you could have by having the surgery now.”

In an interview, Freya Schnabel, MD, director of breast surgery at NYU Langone Health’s Perlmutter Cancer Center, New York City, emphasized the importance of early, well-informed decision-making upfront at the time of diagnosis in this patient population.

The benefit of “risk-reducing oophorectomy cannot be overemphasized, even in the presence of a known breast cancer because, as my colleagues and I say — we don’t want to cure their breast cancer and then have them die of ovarian cancer,” said Schnabel, who was not involved in the study.

In terms of prophylactic contralateral mastectomy, Schnabel noted that BRCA-mutation carriers have a “very high” risk for a second primary breast cancer. In her experience, “that’s what drives patients frequently at the time of diagnosis to have bilateral mastectomy because who wants to go through this more than once?” 

This is especially true for BRCA1 carriers who have a higher risk for triple-negative breast cancer, which is associated with a worse prognosis and is harder to treat, Schnabel said. 

“For these patients, having surgery prevents the patient from getting into a situation where their second primary tumor winds up being biologically more aggressive and then affects their survival,” Schnabel said.

The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Lambertini reported advisory roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, and Menarini. Lathrop consults for TeraSera Pharmaceuticals. Schnabel had no relevant disclosures.

A version of this article first appeared on Medscape.com.

TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

• Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
• To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
• Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
• Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

• Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
• Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
• Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
• Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

• Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
• To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
• Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
• Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

• Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
• Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
• Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
• Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The use of active surveillance or watchful waiting increased by more than twofold overall between 2010 and 2020 among patients with intermediate-risk prostate cancer.

METHODOLOGY:

• Current guidelines support active surveillance or watchful waiting for select patients with intermediate-risk prostate cancer. These observation strategies may help reduce the adverse effects associated with immediate radical treatment.
• To understand the trends over time in the use of active surveillance and watchful waiting, researchers looked at data of 147,205 individuals with intermediate-risk prostate cancer from the Surveillance, Epidemiology, and End Results prostate cancer database between 2010 and 2020 in the United States.
• Criteria for intermediate-risk included Gleason grade group 2 or 3, prostate-specific antigen (PSA) levels of 10-20 ng/mL, or stage cT2b of the disease. Researchers also included trends for patients with Gleason grade group 1, as a reference group.
• Researchers assessed the temporal trends and factors associated with the selection of active surveillance and watchful waiting in this population.

TAKEAWAY:

• Overall, the rate of active surveillance and watchful waiting more than doubled among intermediate-risk patients from 5% to 12.3% between 2010 and 2020.
• Between 2010 and 2020, the use of active surveillance and watchful waiting increased significantly among patients in Gleason grade group 1 (13.2% to 53.8%) and Gleason grade group 2 (4.0% to 11.6%) but remained stable for those in Gleason grade group 3 (2.5% to 2.8%; P = .85). For those with PSA levels < 10 ng/mL, adoption increased from 3.4% in 2010 to 9.2% in 2020 and more than doubled (9.3% to 20.7%) for those with PSA levels of 10-20 ng/mL.
• Higher Gleason grade groups had a significantly lower likelihood of adopting active surveillance or watchful waiting (Gleason grade group 2 vs 1: odds ratio [OR], 0.83; Gleason grade group 3 vs 1: OR, 0.79).
• Hispanic or Latino individuals (OR, 0.98) and non-Hispanic Black individuals (OR, 0.99) were slightly less likely to adopt these strategies than non-Hispanic White individuals.

IN PRACTICE:

“This study found a significant increase in initial active surveillance and watchful waiting for intermediate-risk prostate cancer between 2010 and 2020,” the authors wrote. “Research priorities should include reducing upfront overdiagnosis and better defining criteria for starting and stopping active surveillance and watchful waiting beyond conventional clinical measures such as GGs [Gleason grade groups] or PSA levels alone.”

SOURCE:

This study, led by Ismail Ajjawi, Yale School of Medicine, New Haven, Connecticut, was published online in JAMA.

LIMITATIONS:

This study relied on observational data and therefore could not capture various factors influencing clinical decision-making processes. Additionally, the absence of information on patient outcomes restricted the ability to assess the long-term implications of different management strategies.

DISCLOSURES:

This study received financial support from the Urological Research Foundation. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

A version of this article first appeared on Medscape.com.

More than a third of all patients with cancer die in hospitals, a figure that has increased slightly in recent years, while deaths at home have decreased. These findings come from a recent study published in Cancer Epidemiology, which analyzed data on the different places in Italy where end of life occurs.

“Place of death is relevant both for individuals and for the society. Home is universally considered the optimal place of death, while dying in a hospital may be a signal of inappropriate end-of-life care,” wrote the authors, led by Gianmauro Numico, MD, head of the Oncology Department at the Santa Croce e Carle General Hospital in Cuneo, Italy.

“Despite the general trend toward strengthening community-based networks and the increasing number of hospice and long-term care facilities, we oncologists are facing an opposite trend, with many patients spending their last days in the hospital,” Numico explained to Univadis Italy. This observation led to the questions that prompted the study: Is this only a perception among doctors, or is it a real phenomenon? If the latter, why is it happening? As the expert points out, it is a commonly held belief that people today should not die in the hospital, and numerous studies conducted on healthy individuals suggest that 70%-80% of the population would prefer to die at home.

 

What’s Preferable

For their analysis, Numico and colleagues relied on death certificates published by the Italian National Institute of Statistics from 2015 to 2019, excluding data from the pandemic years to avoid potential biases.

The analysis of data pertaining to cancer deaths revealed that approximately 35% of Italian patients with cancer die in hospitals, with a slight increase over the study period. Of the patients who die elsewhere, 40% die at home and 20% die in hospice or other long-term care facilities. Home deaths have decreased by 3.09%, while those in hospices and long-term care facilities have increased by 2.71%, and hospital deaths have risen by 0.3%.

The study also highlighted notable geographical differences: Hospital deaths are more frequent in the north, while in the south, home deaths remain predominant, although hospital admissions are on the rise. “These differences reflect not only access to facilities but also cultural and social variables,” explained Numico. “Some end-of-life issues with cancer patients are more straightforward, while others are difficult to manage outside the hospital,” he said, recalling that many family members and caregivers are afraid they won’t be able to care for their loved ones properly without the support of an appropriate facility and skilled personnel.

Social factors also contribute to the increased use of hospitals for end-of-life care: Without a social and family network, it is often impossible to manage the final stages of life at home. “We cannot guarantee that dying at home is better for everyone; in some cases, the home cannot provide the necessary care and emotional support,” Numico added.

 

Attitudes Need Change

Looking beyond Italy, it is clear that this trend exists in other countries as well. For example, in the Netherlands — where community-based care is highly developed and includes practices such as euthanasia — hospital death rates are higher than those in Italy. In the United States, the trend is different, but this is largely due to the structure of the US healthcare system, where patients bear much of the financial burden of hospital admissions.

“The basic requests of patients and families are clear: They want a safe place that is adequately staffed and where the patient won’t suffer,” said Numico, questioning whether the home is truly the best place to die. “In reality, this is not always the case, and it’s important to focus on the quality of care in the final days rather than just the place of care,” he added.

Ruling out hospitals a priori as a place to die is not a winning strategy, according to the expert. Instead of trying to reverse the trend, he suggests integrating the hospital into a care network that prioritizes the patient’s well-being, regardless of the setting. “Our goal should not be to eliminate hospital deaths — a common request from hospital administrations — but rather to ensure that end-of-life care in hospitals is a dignified experience that respects the needs of the dying and their loved ones,” Numico said. “We must ensure that, wherever the end-of-life process occurs, it should happen in the best way possible, and the hospital must be a part of this overall framework,” he concluded.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

More than a third of all patients with cancer die in hospitals, a figure that has increased slightly in recent years, while deaths at home have decreased. These findings come from a recent study published in Cancer Epidemiology, which analyzed data on the different places in Italy where end of life occurs.

“Place of death is relevant both for individuals and for the society. Home is universally considered the optimal place of death, while dying in a hospital may be a signal of inappropriate end-of-life care,” wrote the authors, led by Gianmauro Numico, MD, head of the Oncology Department at the Santa Croce e Carle General Hospital in Cuneo, Italy.

“Despite the general trend toward strengthening community-based networks and the increasing number of hospice and long-term care facilities, we oncologists are facing an opposite trend, with many patients spending their last days in the hospital,” Numico explained to Univadis Italy. This observation led to the questions that prompted the study: Is this only a perception among doctors, or is it a real phenomenon? If the latter, why is it happening? As the expert points out, it is a commonly held belief that people today should not die in the hospital, and numerous studies conducted on healthy individuals suggest that 70%-80% of the population would prefer to die at home.

 

What’s Preferable

For their analysis, Numico and colleagues relied on death certificates published by the Italian National Institute of Statistics from 2015 to 2019, excluding data from the pandemic years to avoid potential biases.

The analysis of data pertaining to cancer deaths revealed that approximately 35% of Italian patients with cancer die in hospitals, with a slight increase over the study period. Of the patients who die elsewhere, 40% die at home and 20% die in hospice or other long-term care facilities. Home deaths have decreased by 3.09%, while those in hospices and long-term care facilities have increased by 2.71%, and hospital deaths have risen by 0.3%.

The study also highlighted notable geographical differences: Hospital deaths are more frequent in the north, while in the south, home deaths remain predominant, although hospital admissions are on the rise. “These differences reflect not only access to facilities but also cultural and social variables,” explained Numico. “Some end-of-life issues with cancer patients are more straightforward, while others are difficult to manage outside the hospital,” he said, recalling that many family members and caregivers are afraid they won’t be able to care for their loved ones properly without the support of an appropriate facility and skilled personnel.

Social factors also contribute to the increased use of hospitals for end-of-life care: Without a social and family network, it is often impossible to manage the final stages of life at home. “We cannot guarantee that dying at home is better for everyone; in some cases, the home cannot provide the necessary care and emotional support,” Numico added.

 

Attitudes Need Change

Looking beyond Italy, it is clear that this trend exists in other countries as well. For example, in the Netherlands — where community-based care is highly developed and includes practices such as euthanasia — hospital death rates are higher than those in Italy. In the United States, the trend is different, but this is largely due to the structure of the US healthcare system, where patients bear much of the financial burden of hospital admissions.

“The basic requests of patients and families are clear: They want a safe place that is adequately staffed and where the patient won’t suffer,” said Numico, questioning whether the home is truly the best place to die. “In reality, this is not always the case, and it’s important to focus on the quality of care in the final days rather than just the place of care,” he added.

Ruling out hospitals a priori as a place to die is not a winning strategy, according to the expert. Instead of trying to reverse the trend, he suggests integrating the hospital into a care network that prioritizes the patient’s well-being, regardless of the setting. “Our goal should not be to eliminate hospital deaths — a common request from hospital administrations — but rather to ensure that end-of-life care in hospitals is a dignified experience that respects the needs of the dying and their loved ones,” Numico said. “We must ensure that, wherever the end-of-life process occurs, it should happen in the best way possible, and the hospital must be a part of this overall framework,” he concluded.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

More than a third of all patients with cancer die in hospitals, a figure that has increased slightly in recent years, while deaths at home have decreased. These findings come from a recent study published in Cancer Epidemiology, which analyzed data on the different places in Italy where end of life occurs.

“Place of death is relevant both for individuals and for the society. Home is universally considered the optimal place of death, while dying in a hospital may be a signal of inappropriate end-of-life care,” wrote the authors, led by Gianmauro Numico, MD, head of the Oncology Department at the Santa Croce e Carle General Hospital in Cuneo, Italy.

“Despite the general trend toward strengthening community-based networks and the increasing number of hospice and long-term care facilities, we oncologists are facing an opposite trend, with many patients spending their last days in the hospital,” Numico explained to Univadis Italy. This observation led to the questions that prompted the study: Is this only a perception among doctors, or is it a real phenomenon? If the latter, why is it happening? As the expert points out, it is a commonly held belief that people today should not die in the hospital, and numerous studies conducted on healthy individuals suggest that 70%-80% of the population would prefer to die at home.

 

What’s Preferable

For their analysis, Numico and colleagues relied on death certificates published by the Italian National Institute of Statistics from 2015 to 2019, excluding data from the pandemic years to avoid potential biases.

The analysis of data pertaining to cancer deaths revealed that approximately 35% of Italian patients with cancer die in hospitals, with a slight increase over the study period. Of the patients who die elsewhere, 40% die at home and 20% die in hospice or other long-term care facilities. Home deaths have decreased by 3.09%, while those in hospices and long-term care facilities have increased by 2.71%, and hospital deaths have risen by 0.3%.

The study also highlighted notable geographical differences: Hospital deaths are more frequent in the north, while in the south, home deaths remain predominant, although hospital admissions are on the rise. “These differences reflect not only access to facilities but also cultural and social variables,” explained Numico. “Some end-of-life issues with cancer patients are more straightforward, while others are difficult to manage outside the hospital,” he said, recalling that many family members and caregivers are afraid they won’t be able to care for their loved ones properly without the support of an appropriate facility and skilled personnel.

Social factors also contribute to the increased use of hospitals for end-of-life care: Without a social and family network, it is often impossible to manage the final stages of life at home. “We cannot guarantee that dying at home is better for everyone; in some cases, the home cannot provide the necessary care and emotional support,” Numico added.

 

Attitudes Need Change

Looking beyond Italy, it is clear that this trend exists in other countries as well. For example, in the Netherlands — where community-based care is highly developed and includes practices such as euthanasia — hospital death rates are higher than those in Italy. In the United States, the trend is different, but this is largely due to the structure of the US healthcare system, where patients bear much of the financial burden of hospital admissions.

“The basic requests of patients and families are clear: They want a safe place that is adequately staffed and where the patient won’t suffer,” said Numico, questioning whether the home is truly the best place to die. “In reality, this is not always the case, and it’s important to focus on the quality of care in the final days rather than just the place of care,” he added.

Ruling out hospitals a priori as a place to die is not a winning strategy, according to the expert. Instead of trying to reverse the trend, he suggests integrating the hospital into a care network that prioritizes the patient’s well-being, regardless of the setting. “Our goal should not be to eliminate hospital deaths — a common request from hospital administrations — but rather to ensure that end-of-life care in hospitals is a dignified experience that respects the needs of the dying and their loved ones,” Numico said. “We must ensure that, wherever the end-of-life process occurs, it should happen in the best way possible, and the hospital must be a part of this overall framework,” he concluded.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Chronic pain is one of the most prevalent public health concerns in the United States, affecting > 51 million adults with about $500 billion in health care costs.¹ Military veterans are among the most vulnerable subpopulations, with 65% of veterans reporting chronic pain in the last 3 months.² Chronic pain is complex, affecting the biopsychosocial-spiritual levels of human health, and requires multimodal and comprehensive treatment approaches.³ Hence, chronic pain treatment can be best delivered via interdisciplinary teams (IDTs) that use a patient-centered approach.^4,5

The Veterans Healthcare Administration (VHA) is a leader in developing and delivering interdisciplinary pain care.^6,7 VHA Directive 2009-053 requires every US Department of Veterans Affairs (VA) medical center to offer an IDT for chronic pain. However, VHA and non-VHA IDT programs vary significantly.^8-11 A recent systematic review found a median of 5 disciplines included on IDTs (range, 2-8), and program content often included exercise and education; only 11% of included IDTs met simultaneously with patients.¹¹ The heterogeneity of IDT programs has made determining best practices challenging.^8,11 The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials has denoted several core measures and measurement domains that were critical for determining the success of pain management interventions, including patient satisfaction.^12,13 Nevertheless, the association of IDTs with high patient satisfaction and improvement in pain measures has been documented.^5,11

The VHA has worked to implement the Whole Health System into health care, which considers well-being across physical, behavioral, spiritual, and socioeconomic domains. As such, the Whole Health System involves an interpersonal, team-based approach, “anchored in trusting longitudinal relationships to promote resilience, prevent disease, and restore health.”¹⁴ It aligns with the patient’s mission, aspiration, and purpose. Surgeon General VADM Vivek H. Murthy, MD, MBA, recently endorsed this approach.^15,16 Other health care systems adopting whole health tend to have higher patient satisfaction, increased access to care, and improved patient-reported outcomes.¹⁵ Within the VHA, the Whole Health System has shifted the conversation between clinicians and patients from “What is the matter with you?” to “What is important to you?” while emphasizing a proactive and personalized approach to health care.¹⁷ Rather than emphasizing passive modalities such as medications and clinician-led services (eg, interventional pain service), the Whole Health System highlights self-care.^3,17 Initial research findings within the VHA have been promising.^18-21 Whole health peer coaching calls appear to be an effective approach for veterans diagnosed with PTSD, and the use of whole health services is associated with a decrease in opioid use.^19,22 However, there are negligible data on patient experiences after meeting with a whole health-focused pain IDT, and studies to date have focused on urban populations.²³ One approach to IDT that has shown promise for other health issues involves a patient meeting simultaneously with all members of the IDT.^24-27 With the integration of the Whole Health System and the VHA priorities to provide veterans with the “soonest and best care,” more data are needed on the experiences of patients and support persons with various approaches to IDT pain care.²⁸ This study aimed to evaluate patient and support person experiences with a whole health-focused pain IDT that met simultaneously with the patient and support person during an initial evaluation. This study was approved by the institutional review board at the Salem VA Health Care System (SVAHCS) in Virginia.

Methods

The PREVAIL IDT Track is a clinical program offered at SVAHCS with a whole health-focused approach that involves patients and their support persons meeting simultaneously with a pain IDT. PREVAIL IDT Track is designed to help veterans more effectively self-manage chronic pain (Table 1).^6,29 Health care practitioners (HCPs) at SVAHCS recommended that veterans with pain persisting for > 3 months participate in PREVAIL IDT Track. After meeting with an advanced practice clinician for an intake, veterans elected to participate in the PREVAIL IDT Track program and completed the initial 6 weeks of pain education. Veterans were then invited to be evaluated by the pain IDT. A team including HCPs from interventional pain, psychology, pharmacy, nutrition, and physical therapy services met with the veteran for 60 minutes. Veterans were also invited to bring a support person to the IDT initial evaluation.

During the IDT initial evaluation, HCPs inquired about the patient’s mission, aspiration, and purpose (“If you were in less pain, what would you be doing more of?”) and about whole health self-care and wellness factors that may contribute to their chronic pain using the Personal Health Inventory.^30,31 Veterans were then invited to select 3 whole health self-care areas to focus on during the 6-month program.³ The IDT HCPs worked with the veteran to establish the treatment plan for the first month in the areas of self-care selected by the patient and made recommendations for additional treatments. If the veteran brought a support person to the IDT initial evaluation, their feedback was elicited throughout and at the end to ensure the final treatment plan and first month’s goals were realistic. At the end of the appointment, the veteran and their support person were asked to complete a program-specific satisfaction survey. The HCPs on the team and the veteran executed the treatment plan developed during the appointment, except for medication prescribing. Recommendations for medication changes are included in clinical notes. Veterans then received 5 monthly coaching calls from a nurse navigator with training in whole health and a 6-month follow-up appointment with the IDT HCPs to discuss a plan for continuity of care.

Participant demographic information was not collected, and participants were not compensated for completing the survey. Veterans in PREVAIL IDT Track are predominantly residents of central Appalachia, White, male, unemployed, have ≥ 1 mental and physical health comorbidity, and have a history of mental health treatment.³² Veterans participating in PREVAIL IDT had a mean age of 57 years, and about 1 in 3 have opioid prescriptions.³²

A program-specific 17-question satisfaction survey was developed, which included questions related to satisfaction with previous SVAHCS pain care and staff interactions. To assess the overall impression of the IDT initial evaluation, 3 yes/no questions and a 0 to 10-point scale were used. The 5 remaining open-ended questions allowed participants to give feedback about the IDT initial evaluation.

Data Analysis

A convergent mixed-methods approach was used to evaluate participant satisfaction with the initial IDT evaluation. The study team collected and analyzed quantitative and qualitative survey data and triangulated the findings.³³ For quantitative responses, frequencies and means were calculated using Python. For qualitative responses, thematic data analysis was conducted by systematic coding, using inductive methods and allowing themes to emerge. Study team members performed a line-by-line analysis of responses using NVivo to identify important codes and reach a consensus. This study adhered to the Consolidated Criteria for Reporting Qualitative Research and followed the National Institute for Health Care Excellence checklist.^34,35

Results

Quantitative Responses

In 2022, 168 veterans completed the initial IDT evaluation, and 144 (85.2%) completed the satisfaction survey and were included in this study. Thirty-two support persons who attended the initial IDT evaluation and completed the survey also were included. Of the 12 quantitative questions, 4 had a 100% completion rate, while 8 had ≤ 3% missing responses. When describing care prior to participating in PREVAIL, participants indicated a mean (SD) response of 4.6 (1.4) with the health care they received at SVAHCS and 4.3 (1.4) with SVAHCS pain management services, both on 6-point scales. All but 2 participants (98.9%) reported always being treated with courtesy and respect by PREVAIL HCPs during the initial IDT evaluation, with a mean (SD) score of 4.0 (0.2) on a 4-point scale. Most respondents (96.6%) reported that PREVAIL HCPs always listened carefully during the initial IDT evaluation, with a mean (SD) 4.0 (0.3) on a 4-point scale. Similarly, 92.6% reported that PREVAIL HCPs explained things clearly during the initial IDT evaluation, with a mean (SD) 3.9 (0.3) on a 4-point scale.

All respondents agreed that PREVAIL HCPs considered veteran preferences and those of their support persons in deciding their health care needs during the initial IDT evaluation, with a mean (SD) 3.7 (0.5) on a 4-point scale. Most respondents left the appointment with a good understanding of their responsibilities for chronic pain management with 99.4% (n = 169) strongly agreeing or agreeing (mean [SD] 3.6 [0.5]). A total of 135 respondents (79.4%) reported they left appointments with written information on their treatment plan. All 170 respondents reported that they would recommend PREVAIL to a friend, and 169 respondents (98.8%) felt that the initial PREVAIL IDT evaluation was a valuable use of time. Eighty-seven respondents (50.9%) rated the initial IDT evaluation as the “best clinical experience possible” with a mean (SD) score of 9.2 (1.1) on a 10-point scale (Table 2).

Qualitative Responses

Respondents provided complementary feedback on the program, with many participants stating that they enjoyed every aspect (eAppendix, available at doi:10.12788/fp.0503). In terms of positive aspects of the program, several themes emerged: participants appreciated meeting as an IDT, feeling cared for and listened to, learning more about their pain and ways to manage it, and specific services offered. Thirty-three of 144 respondents wanted longer appointment times. Twenty-two respondents suggested logistics improvements (eg, meeting in a larger room, having a written plan at the end, sending paperwork ahead of time, and later appointment times).

Discussion

Veterans and support persons were satisfied with the initial IDT evaluation for the PREVAIL whole health-focused pain clinical program for veterans predominantly residing in central Appalachia. These satisfaction findings are noteworthy since 20% of this same sample reported dissatisfaction with prior pain services, which could affect engagement and outcomes in pain care. In addition to high satisfaction levels, the PREVAIL IDT model may benefit veterans with limited resources. Rather than needing to attend several individual appointments, the PREVAIL IDT Track provides a 1-stop shop approach that decreases patient burden and barriers to care (eg, travel, transportation, and time) as well as health care system burden. For instance, schedulers need only to make 1 appointment for the veteran rather than several. This approach was highly acceptable to veterans served at SVAHCS and may increase the reach and impact of VHA IDT pain care.

The PREVAIL model may foster rapport with HCPs and encourage an active role in self-managing pain.^36,37 Participants noted that their preferences were considered and that they had a good understanding of their responsibilities for managing their chronic pain. This patient-centered approach, emphasizing an active role for the patient, is a hallmark of the VHA Whole Health System and aligns with the overarching PREVAIL IDT Track goal to enhance self-management skills, thus improving functioning through decreased pain interference.^14,38-41

Participants in PREVAIL provided substantial open-ended feedback that has contributed to the program’s improvement and may provide information into preferred components of pain IDT programs, particularly for rural veterans. When asked about their favorite component of the initial IDT evaluation, the most emergent theme was meeting simultaneously with HCPs on the IDT. This finding is significant, given that only 11% of IDTs involve direct patient interaction.

Furthermore, unlike most IDTs, PREVAIL IDT includes a dietitian.^11,42 IDT programs may benefit from dietitian involvement given the importance of the anti-inflammatory diet on chronic pain.^43-46 Participants recommended improvements, (eg, changes to the location and timing, adding a written treatment plan at the end of the appointment, and completing paperwork prior to the appointment) many of which have been addressed. The program now uses validated measures to track progress and comprehensive assessments of pain in response to calls for measurement-based care.^13,47 These process improvement suggestions may be instructive for other VA medical centers with rural populations.

Limitations

This study used a program-specific satisfaction survey with open-ended questions to allow for rich responses; however, the survey has not been validated. It also sought to minimize bias by asking participants to give completed surveys to staff members who were not HCPs on the IDT. However, participants’ responses may still have been influenced by this process. Response rate and demographics for support persons were impossible to determine. The results analyzed the responses of veterans and support persons together, which may have skewed the data. Future studies of pain IDT programs should consider analyzing responses from veterans and their support persons separately and identifying factors (eg, demographics or clinical characteristics) that influence the patients’ experiences while participating.

Conclusions

The initial PREVAIL IDT evaluation at SVAHCS is associated with high-levels of satisfaction. These veterans living in rural Appalachia, similar to the 4.4 million rural US veterans, are more likely to encounter barriers to care (eg, drive time, or transportation concerns) and be prescribed opioids.⁴⁸ These veterans are also at high risk of chronic physical and mental health comorbidities, drug misuse, overdose, and suicide.^49,50 Providing veterans in rural communities the opportunity to attend a single appointment with a pain IDT instead of requiring several individual appointments could improve the reach of evidence-based pain care.

This model of meeting simultaneously with all HCPs on the pain IDT may connect all veterans to the most available and best care, something prioritized by the VHA.28 The initial PREVAIL IDT evaluation also utilizes the Personal Health Inventory and the VHA Whole Health System Circle of Health to design patient-centered treatment plans. Integration of the Whole Health System is currently a high priority within VHA. The PREVAIL IDT Track model warrants additional efficacy research.

Chronic pain is one of the most prevalent public health concerns in the United States, affecting > 51 million adults with about $500 billion in health care costs.¹ Military veterans are among the most vulnerable subpopulations, with 65% of veterans reporting chronic pain in the last 3 months.² Chronic pain is complex, affecting the biopsychosocial-spiritual levels of human health, and requires multimodal and comprehensive treatment approaches.³ Hence, chronic pain treatment can be best delivered via interdisciplinary teams (IDTs) that use a patient-centered approach.^4,5

The Veterans Healthcare Administration (VHA) is a leader in developing and delivering interdisciplinary pain care.^6,7 VHA Directive 2009-053 requires every US Department of Veterans Affairs (VA) medical center to offer an IDT for chronic pain. However, VHA and non-VHA IDT programs vary significantly.^8-11 A recent systematic review found a median of 5 disciplines included on IDTs (range, 2-8), and program content often included exercise and education; only 11% of included IDTs met simultaneously with patients.¹¹ The heterogeneity of IDT programs has made determining best practices challenging.^8,11 The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials has denoted several core measures and measurement domains that were critical for determining the success of pain management interventions, including patient satisfaction.^12,13 Nevertheless, the association of IDTs with high patient satisfaction and improvement in pain measures has been documented.^5,11

The VHA has worked to implement the Whole Health System into health care, which considers well-being across physical, behavioral, spiritual, and socioeconomic domains. As such, the Whole Health System involves an interpersonal, team-based approach, “anchored in trusting longitudinal relationships to promote resilience, prevent disease, and restore health.”¹⁴ It aligns with the patient’s mission, aspiration, and purpose. Surgeon General VADM Vivek H. Murthy, MD, MBA, recently endorsed this approach.^15,16 Other health care systems adopting whole health tend to have higher patient satisfaction, increased access to care, and improved patient-reported outcomes.¹⁵ Within the VHA, the Whole Health System has shifted the conversation between clinicians and patients from “What is the matter with you?” to “What is important to you?” while emphasizing a proactive and personalized approach to health care.¹⁷ Rather than emphasizing passive modalities such as medications and clinician-led services (eg, interventional pain service), the Whole Health System highlights self-care.^3,17 Initial research findings within the VHA have been promising.^18-21 Whole health peer coaching calls appear to be an effective approach for veterans diagnosed with PTSD, and the use of whole health services is associated with a decrease in opioid use.^19,22 However, there are negligible data on patient experiences after meeting with a whole health-focused pain IDT, and studies to date have focused on urban populations.²³ One approach to IDT that has shown promise for other health issues involves a patient meeting simultaneously with all members of the IDT.^24-27 With the integration of the Whole Health System and the VHA priorities to provide veterans with the “soonest and best care,” more data are needed on the experiences of patients and support persons with various approaches to IDT pain care.²⁸ This study aimed to evaluate patient and support person experiences with a whole health-focused pain IDT that met simultaneously with the patient and support person during an initial evaluation. This study was approved by the institutional review board at the Salem VA Health Care System (SVAHCS) in Virginia.

Methods

The PREVAIL IDT Track is a clinical program offered at SVAHCS with a whole health-focused approach that involves patients and their support persons meeting simultaneously with a pain IDT. PREVAIL IDT Track is designed to help veterans more effectively self-manage chronic pain (Table 1).^6,29 Health care practitioners (HCPs) at SVAHCS recommended that veterans with pain persisting for > 3 months participate in PREVAIL IDT Track. After meeting with an advanced practice clinician for an intake, veterans elected to participate in the PREVAIL IDT Track program and completed the initial 6 weeks of pain education. Veterans were then invited to be evaluated by the pain IDT. A team including HCPs from interventional pain, psychology, pharmacy, nutrition, and physical therapy services met with the veteran for 60 minutes. Veterans were also invited to bring a support person to the IDT initial evaluation.

During the IDT initial evaluation, HCPs inquired about the patient’s mission, aspiration, and purpose (“If you were in less pain, what would you be doing more of?”) and about whole health self-care and wellness factors that may contribute to their chronic pain using the Personal Health Inventory.^30,31 Veterans were then invited to select 3 whole health self-care areas to focus on during the 6-month program.³ The IDT HCPs worked with the veteran to establish the treatment plan for the first month in the areas of self-care selected by the patient and made recommendations for additional treatments. If the veteran brought a support person to the IDT initial evaluation, their feedback was elicited throughout and at the end to ensure the final treatment plan and first month’s goals were realistic. At the end of the appointment, the veteran and their support person were asked to complete a program-specific satisfaction survey. The HCPs on the team and the veteran executed the treatment plan developed during the appointment, except for medication prescribing. Recommendations for medication changes are included in clinical notes. Veterans then received 5 monthly coaching calls from a nurse navigator with training in whole health and a 6-month follow-up appointment with the IDT HCPs to discuss a plan for continuity of care.

Participant demographic information was not collected, and participants were not compensated for completing the survey. Veterans in PREVAIL IDT Track are predominantly residents of central Appalachia, White, male, unemployed, have ≥ 1 mental and physical health comorbidity, and have a history of mental health treatment.³² Veterans participating in PREVAIL IDT had a mean age of 57 years, and about 1 in 3 have opioid prescriptions.³²

A program-specific 17-question satisfaction survey was developed, which included questions related to satisfaction with previous SVAHCS pain care and staff interactions. To assess the overall impression of the IDT initial evaluation, 3 yes/no questions and a 0 to 10-point scale were used. The 5 remaining open-ended questions allowed participants to give feedback about the IDT initial evaluation.

Data Analysis

A convergent mixed-methods approach was used to evaluate participant satisfaction with the initial IDT evaluation. The study team collected and analyzed quantitative and qualitative survey data and triangulated the findings.³³ For quantitative responses, frequencies and means were calculated using Python. For qualitative responses, thematic data analysis was conducted by systematic coding, using inductive methods and allowing themes to emerge. Study team members performed a line-by-line analysis of responses using NVivo to identify important codes and reach a consensus. This study adhered to the Consolidated Criteria for Reporting Qualitative Research and followed the National Institute for Health Care Excellence checklist.^34,35

Results

Quantitative Responses

In 2022, 168 veterans completed the initial IDT evaluation, and 144 (85.2%) completed the satisfaction survey and were included in this study. Thirty-two support persons who attended the initial IDT evaluation and completed the survey also were included. Of the 12 quantitative questions, 4 had a 100% completion rate, while 8 had ≤ 3% missing responses. When describing care prior to participating in PREVAIL, participants indicated a mean (SD) response of 4.6 (1.4) with the health care they received at SVAHCS and 4.3 (1.4) with SVAHCS pain management services, both on 6-point scales. All but 2 participants (98.9%) reported always being treated with courtesy and respect by PREVAIL HCPs during the initial IDT evaluation, with a mean (SD) score of 4.0 (0.2) on a 4-point scale. Most respondents (96.6%) reported that PREVAIL HCPs always listened carefully during the initial IDT evaluation, with a mean (SD) 4.0 (0.3) on a 4-point scale. Similarly, 92.6% reported that PREVAIL HCPs explained things clearly during the initial IDT evaluation, with a mean (SD) 3.9 (0.3) on a 4-point scale.

All respondents agreed that PREVAIL HCPs considered veteran preferences and those of their support persons in deciding their health care needs during the initial IDT evaluation, with a mean (SD) 3.7 (0.5) on a 4-point scale. Most respondents left the appointment with a good understanding of their responsibilities for chronic pain management with 99.4% (n = 169) strongly agreeing or agreeing (mean [SD] 3.6 [0.5]). A total of 135 respondents (79.4%) reported they left appointments with written information on their treatment plan. All 170 respondents reported that they would recommend PREVAIL to a friend, and 169 respondents (98.8%) felt that the initial PREVAIL IDT evaluation was a valuable use of time. Eighty-seven respondents (50.9%) rated the initial IDT evaluation as the “best clinical experience possible” with a mean (SD) score of 9.2 (1.1) on a 10-point scale (Table 2).

Qualitative Responses

Respondents provided complementary feedback on the program, with many participants stating that they enjoyed every aspect (eAppendix, available at doi:10.12788/fp.0503). In terms of positive aspects of the program, several themes emerged: participants appreciated meeting as an IDT, feeling cared for and listened to, learning more about their pain and ways to manage it, and specific services offered. Thirty-three of 144 respondents wanted longer appointment times. Twenty-two respondents suggested logistics improvements (eg, meeting in a larger room, having a written plan at the end, sending paperwork ahead of time, and later appointment times).

Discussion

Veterans and support persons were satisfied with the initial IDT evaluation for the PREVAIL whole health-focused pain clinical program for veterans predominantly residing in central Appalachia. These satisfaction findings are noteworthy since 20% of this same sample reported dissatisfaction with prior pain services, which could affect engagement and outcomes in pain care. In addition to high satisfaction levels, the PREVAIL IDT model may benefit veterans with limited resources. Rather than needing to attend several individual appointments, the PREVAIL IDT Track provides a 1-stop shop approach that decreases patient burden and barriers to care (eg, travel, transportation, and time) as well as health care system burden. For instance, schedulers need only to make 1 appointment for the veteran rather than several. This approach was highly acceptable to veterans served at SVAHCS and may increase the reach and impact of VHA IDT pain care.

The PREVAIL model may foster rapport with HCPs and encourage an active role in self-managing pain.^36,37 Participants noted that their preferences were considered and that they had a good understanding of their responsibilities for managing their chronic pain. This patient-centered approach, emphasizing an active role for the patient, is a hallmark of the VHA Whole Health System and aligns with the overarching PREVAIL IDT Track goal to enhance self-management skills, thus improving functioning through decreased pain interference.^14,38-41

Participants in PREVAIL provided substantial open-ended feedback that has contributed to the program’s improvement and may provide information into preferred components of pain IDT programs, particularly for rural veterans. When asked about their favorite component of the initial IDT evaluation, the most emergent theme was meeting simultaneously with HCPs on the IDT. This finding is significant, given that only 11% of IDTs involve direct patient interaction.

Furthermore, unlike most IDTs, PREVAIL IDT includes a dietitian.^11,42 IDT programs may benefit from dietitian involvement given the importance of the anti-inflammatory diet on chronic pain.^43-46 Participants recommended improvements, (eg, changes to the location and timing, adding a written treatment plan at the end of the appointment, and completing paperwork prior to the appointment) many of which have been addressed. The program now uses validated measures to track progress and comprehensive assessments of pain in response to calls for measurement-based care.^13,47 These process improvement suggestions may be instructive for other VA medical centers with rural populations.

Limitations

This study used a program-specific satisfaction survey with open-ended questions to allow for rich responses; however, the survey has not been validated. It also sought to minimize bias by asking participants to give completed surveys to staff members who were not HCPs on the IDT. However, participants’ responses may still have been influenced by this process. Response rate and demographics for support persons were impossible to determine. The results analyzed the responses of veterans and support persons together, which may have skewed the data. Future studies of pain IDT programs should consider analyzing responses from veterans and their support persons separately and identifying factors (eg, demographics or clinical characteristics) that influence the patients’ experiences while participating.

Conclusions

The initial PREVAIL IDT evaluation at SVAHCS is associated with high-levels of satisfaction. These veterans living in rural Appalachia, similar to the 4.4 million rural US veterans, are more likely to encounter barriers to care (eg, drive time, or transportation concerns) and be prescribed opioids.⁴⁸ These veterans are also at high risk of chronic physical and mental health comorbidities, drug misuse, overdose, and suicide.^49,50 Providing veterans in rural communities the opportunity to attend a single appointment with a pain IDT instead of requiring several individual appointments could improve the reach of evidence-based pain care.

This model of meeting simultaneously with all HCPs on the pain IDT may connect all veterans to the most available and best care, something prioritized by the VHA.28 The initial PREVAIL IDT evaluation also utilizes the Personal Health Inventory and the VHA Whole Health System Circle of Health to design patient-centered treatment plans. Integration of the Whole Health System is currently a high priority within VHA. The PREVAIL IDT Track model warrants additional efficacy research.

Chronic pain is one of the most prevalent public health concerns in the United States, affecting > 51 million adults with about $500 billion in health care costs.¹ Military veterans are among the most vulnerable subpopulations, with 65% of veterans reporting chronic pain in the last 3 months.² Chronic pain is complex, affecting the biopsychosocial-spiritual levels of human health, and requires multimodal and comprehensive treatment approaches.³ Hence, chronic pain treatment can be best delivered via interdisciplinary teams (IDTs) that use a patient-centered approach.^4,5

The Veterans Healthcare Administration (VHA) is a leader in developing and delivering interdisciplinary pain care.^6,7 VHA Directive 2009-053 requires every US Department of Veterans Affairs (VA) medical center to offer an IDT for chronic pain. However, VHA and non-VHA IDT programs vary significantly.^8-11 A recent systematic review found a median of 5 disciplines included on IDTs (range, 2-8), and program content often included exercise and education; only 11% of included IDTs met simultaneously with patients.¹¹ The heterogeneity of IDT programs has made determining best practices challenging.^8,11 The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials has denoted several core measures and measurement domains that were critical for determining the success of pain management interventions, including patient satisfaction.^12,13 Nevertheless, the association of IDTs with high patient satisfaction and improvement in pain measures has been documented.^5,11

The VHA has worked to implement the Whole Health System into health care, which considers well-being across physical, behavioral, spiritual, and socioeconomic domains. As such, the Whole Health System involves an interpersonal, team-based approach, “anchored in trusting longitudinal relationships to promote resilience, prevent disease, and restore health.”¹⁴ It aligns with the patient’s mission, aspiration, and purpose. Surgeon General VADM Vivek H. Murthy, MD, MBA, recently endorsed this approach.^15,16 Other health care systems adopting whole health tend to have higher patient satisfaction, increased access to care, and improved patient-reported outcomes.¹⁵ Within the VHA, the Whole Health System has shifted the conversation between clinicians and patients from “What is the matter with you?” to “What is important to you?” while emphasizing a proactive and personalized approach to health care.¹⁷ Rather than emphasizing passive modalities such as medications and clinician-led services (eg, interventional pain service), the Whole Health System highlights self-care.^3,17 Initial research findings within the VHA have been promising.^18-21 Whole health peer coaching calls appear to be an effective approach for veterans diagnosed with PTSD, and the use of whole health services is associated with a decrease in opioid use.^19,22 However, there are negligible data on patient experiences after meeting with a whole health-focused pain IDT, and studies to date have focused on urban populations.²³ One approach to IDT that has shown promise for other health issues involves a patient meeting simultaneously with all members of the IDT.^24-27 With the integration of the Whole Health System and the VHA priorities to provide veterans with the “soonest and best care,” more data are needed on the experiences of patients and support persons with various approaches to IDT pain care.²⁸ This study aimed to evaluate patient and support person experiences with a whole health-focused pain IDT that met simultaneously with the patient and support person during an initial evaluation. This study was approved by the institutional review board at the Salem VA Health Care System (SVAHCS) in Virginia.

Methods

The PREVAIL IDT Track is a clinical program offered at SVAHCS with a whole health-focused approach that involves patients and their support persons meeting simultaneously with a pain IDT. PREVAIL IDT Track is designed to help veterans more effectively self-manage chronic pain (Table 1).^6,29 Health care practitioners (HCPs) at SVAHCS recommended that veterans with pain persisting for > 3 months participate in PREVAIL IDT Track. After meeting with an advanced practice clinician for an intake, veterans elected to participate in the PREVAIL IDT Track program and completed the initial 6 weeks of pain education. Veterans were then invited to be evaluated by the pain IDT. A team including HCPs from interventional pain, psychology, pharmacy, nutrition, and physical therapy services met with the veteran for 60 minutes. Veterans were also invited to bring a support person to the IDT initial evaluation.

During the IDT initial evaluation, HCPs inquired about the patient’s mission, aspiration, and purpose (“If you were in less pain, what would you be doing more of?”) and about whole health self-care and wellness factors that may contribute to their chronic pain using the Personal Health Inventory.^30,31 Veterans were then invited to select 3 whole health self-care areas to focus on during the 6-month program.³ The IDT HCPs worked with the veteran to establish the treatment plan for the first month in the areas of self-care selected by the patient and made recommendations for additional treatments. If the veteran brought a support person to the IDT initial evaluation, their feedback was elicited throughout and at the end to ensure the final treatment plan and first month’s goals were realistic. At the end of the appointment, the veteran and their support person were asked to complete a program-specific satisfaction survey. The HCPs on the team and the veteran executed the treatment plan developed during the appointment, except for medication prescribing. Recommendations for medication changes are included in clinical notes. Veterans then received 5 monthly coaching calls from a nurse navigator with training in whole health and a 6-month follow-up appointment with the IDT HCPs to discuss a plan for continuity of care.

Participant demographic information was not collected, and participants were not compensated for completing the survey. Veterans in PREVAIL IDT Track are predominantly residents of central Appalachia, White, male, unemployed, have ≥ 1 mental and physical health comorbidity, and have a history of mental health treatment.³² Veterans participating in PREVAIL IDT had a mean age of 57 years, and about 1 in 3 have opioid prescriptions.³²

A program-specific 17-question satisfaction survey was developed, which included questions related to satisfaction with previous SVAHCS pain care and staff interactions. To assess the overall impression of the IDT initial evaluation, 3 yes/no questions and a 0 to 10-point scale were used. The 5 remaining open-ended questions allowed participants to give feedback about the IDT initial evaluation.

Data Analysis

A convergent mixed-methods approach was used to evaluate participant satisfaction with the initial IDT evaluation. The study team collected and analyzed quantitative and qualitative survey data and triangulated the findings.³³ For quantitative responses, frequencies and means were calculated using Python. For qualitative responses, thematic data analysis was conducted by systematic coding, using inductive methods and allowing themes to emerge. Study team members performed a line-by-line analysis of responses using NVivo to identify important codes and reach a consensus. This study adhered to the Consolidated Criteria for Reporting Qualitative Research and followed the National Institute for Health Care Excellence checklist.^34,35

Results

Quantitative Responses

In 2022, 168 veterans completed the initial IDT evaluation, and 144 (85.2%) completed the satisfaction survey and were included in this study. Thirty-two support persons who attended the initial IDT evaluation and completed the survey also were included. Of the 12 quantitative questions, 4 had a 100% completion rate, while 8 had ≤ 3% missing responses. When describing care prior to participating in PREVAIL, participants indicated a mean (SD) response of 4.6 (1.4) with the health care they received at SVAHCS and 4.3 (1.4) with SVAHCS pain management services, both on 6-point scales. All but 2 participants (98.9%) reported always being treated with courtesy and respect by PREVAIL HCPs during the initial IDT evaluation, with a mean (SD) score of 4.0 (0.2) on a 4-point scale. Most respondents (96.6%) reported that PREVAIL HCPs always listened carefully during the initial IDT evaluation, with a mean (SD) 4.0 (0.3) on a 4-point scale. Similarly, 92.6% reported that PREVAIL HCPs explained things clearly during the initial IDT evaluation, with a mean (SD) 3.9 (0.3) on a 4-point scale.

All respondents agreed that PREVAIL HCPs considered veteran preferences and those of their support persons in deciding their health care needs during the initial IDT evaluation, with a mean (SD) 3.7 (0.5) on a 4-point scale. Most respondents left the appointment with a good understanding of their responsibilities for chronic pain management with 99.4% (n = 169) strongly agreeing or agreeing (mean [SD] 3.6 [0.5]). A total of 135 respondents (79.4%) reported they left appointments with written information on their treatment plan. All 170 respondents reported that they would recommend PREVAIL to a friend, and 169 respondents (98.8%) felt that the initial PREVAIL IDT evaluation was a valuable use of time. Eighty-seven respondents (50.9%) rated the initial IDT evaluation as the “best clinical experience possible” with a mean (SD) score of 9.2 (1.1) on a 10-point scale (Table 2).

Qualitative Responses

Respondents provided complementary feedback on the program, with many participants stating that they enjoyed every aspect (eAppendix, available at doi:10.12788/fp.0503). In terms of positive aspects of the program, several themes emerged: participants appreciated meeting as an IDT, feeling cared for and listened to, learning more about their pain and ways to manage it, and specific services offered. Thirty-three of 144 respondents wanted longer appointment times. Twenty-two respondents suggested logistics improvements (eg, meeting in a larger room, having a written plan at the end, sending paperwork ahead of time, and later appointment times).

Discussion

Veterans and support persons were satisfied with the initial IDT evaluation for the PREVAIL whole health-focused pain clinical program for veterans predominantly residing in central Appalachia. These satisfaction findings are noteworthy since 20% of this same sample reported dissatisfaction with prior pain services, which could affect engagement and outcomes in pain care. In addition to high satisfaction levels, the PREVAIL IDT model may benefit veterans with limited resources. Rather than needing to attend several individual appointments, the PREVAIL IDT Track provides a 1-stop shop approach that decreases patient burden and barriers to care (eg, travel, transportation, and time) as well as health care system burden. For instance, schedulers need only to make 1 appointment for the veteran rather than several. This approach was highly acceptable to veterans served at SVAHCS and may increase the reach and impact of VHA IDT pain care.

The PREVAIL model may foster rapport with HCPs and encourage an active role in self-managing pain.^36,37 Participants noted that their preferences were considered and that they had a good understanding of their responsibilities for managing their chronic pain. This patient-centered approach, emphasizing an active role for the patient, is a hallmark of the VHA Whole Health System and aligns with the overarching PREVAIL IDT Track goal to enhance self-management skills, thus improving functioning through decreased pain interference.^14,38-41

Participants in PREVAIL provided substantial open-ended feedback that has contributed to the program’s improvement and may provide information into preferred components of pain IDT programs, particularly for rural veterans. When asked about their favorite component of the initial IDT evaluation, the most emergent theme was meeting simultaneously with HCPs on the IDT. This finding is significant, given that only 11% of IDTs involve direct patient interaction.

Furthermore, unlike most IDTs, PREVAIL IDT includes a dietitian.^11,42 IDT programs may benefit from dietitian involvement given the importance of the anti-inflammatory diet on chronic pain.^43-46 Participants recommended improvements, (eg, changes to the location and timing, adding a written treatment plan at the end of the appointment, and completing paperwork prior to the appointment) many of which have been addressed. The program now uses validated measures to track progress and comprehensive assessments of pain in response to calls for measurement-based care.^13,47 These process improvement suggestions may be instructive for other VA medical centers with rural populations.

Limitations

This study used a program-specific satisfaction survey with open-ended questions to allow for rich responses; however, the survey has not been validated. It also sought to minimize bias by asking participants to give completed surveys to staff members who were not HCPs on the IDT. However, participants’ responses may still have been influenced by this process. Response rate and demographics for support persons were impossible to determine. The results analyzed the responses of veterans and support persons together, which may have skewed the data. Future studies of pain IDT programs should consider analyzing responses from veterans and their support persons separately and identifying factors (eg, demographics or clinical characteristics) that influence the patients’ experiences while participating.

Conclusions

The initial PREVAIL IDT evaluation at SVAHCS is associated with high-levels of satisfaction. These veterans living in rural Appalachia, similar to the 4.4 million rural US veterans, are more likely to encounter barriers to care (eg, drive time, or transportation concerns) and be prescribed opioids.⁴⁸ These veterans are also at high risk of chronic physical and mental health comorbidities, drug misuse, overdose, and suicide.^49,50 Providing veterans in rural communities the opportunity to attend a single appointment with a pain IDT instead of requiring several individual appointments could improve the reach of evidence-based pain care.

This model of meeting simultaneously with all HCPs on the pain IDT may connect all veterans to the most available and best care, something prioritized by the VHA.28 The initial PREVAIL IDT evaluation also utilizes the Personal Health Inventory and the VHA Whole Health System Circle of Health to design patient-centered treatment plans. Integration of the Whole Health System is currently a high priority within VHA. The PREVAIL IDT Track model warrants additional efficacy research.