Breast Cancer ICYMI

CHICAGO – Adding ribociclib to endocrine therapy significantly improved overall survival of premenopausal women with advanced hormone receptor positive, HER2-negative breast cancer, results of the randomized phase 3 MONALEESA-7 trial showed.

Neil Osterweil/MDedge News

A landmark analysis conducted at 42 months showed that the overall survival rate for women randomized to receive endocrine therapy with either a nonsteroidal aromatase inhibitor (AI) or tamoxifen plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib was 70%, compared with 46% for women randomized to endocrine therapy alone, reported Sara A Hurvitz, MD, of the University of California Los Angeles Jonsson Comprehensive Cancer Center

“This is the first time a statistically significant improvement in overall survival has been observed with a CDK4/6 inhibitor in combination with endocrine therapy in patients with hormone receptor-positive advanced disease,” she said at a briefing prior to her presentation of the data in an oral abstract session at the American Society of Clinical Oncology annual meeting.

“This is an important study, because it shows that the class of drugs, CDK4/6 inhibitors, which we are widely using, has been shown to delay the time to progression, delay the time to need for chemotherapy for advanced breast cancer, and really doubled the effectiveness of endocrine therapy, now also translates into a significant survival benefit for women who ER-positive metastatic breast cancer,” commented Harold J. Burstein, MD, PhD, an ASCO expert from the Dana-Farber Cancer Institute in Boston.

Neil Osterweil/MDedge News

In the trial, 672 pre- or perimenopausal women with HR+/HER2– advanced breast cancer with no prior endocrine therapy for advanced disease and no more than one line of chemotherapy for advanced disease were enrolled. The patients were stratified by the presence of liver/lung metastases, prior chemotherapy, and prior endocrine partner, tamoxifen or nonsteroidal AI, and then randomly assigned to ribociclib 600 mg/day for 3 weeks, followed by 1-week off, plus tamoxifen or AI and goserelin, or the same combination and schedule with placebo.

Of the 672 patients enrolled, a total of 335 patients assigned to ribociclib and 337 assigned to placebo received treatment. The majority of patients – 495 – received an AI, either letrozole (Femara) or anastrozole (Arimidex). Dr. Hurvitz noted that after the initiation of MONALEESA-7, the combination of a CDK4/6 inhibitor and tamoxifen was found to prolong the QT interval and increase risk for cardiac arrhythmias, and is now contraindicated.

As previously reported , results of the primary MONALEESA-7 endpoint of progression-free survival favored the combination, with a median PFS of 23.8 months, compared with 13 months for women treated with endocrine therapy alone. The hazard ratio for progression with the ribociclib-based combination was 0.553 ( P less than .0001), and the treatment benefit of the CDK4/6 inhibitor was seen across all patients subgroups and regardless of the endocrine partner.

At ASCO 2019, Dr. Hurvitz reported on the key secondary endpoint of overall survival. At a median follow-up duration of 34.6 months, with an additional 15 months beyond the initial analysis, the median OS for the ribociclib arm was not reached, compared with 40.9 months in the placebo arm. The hazard ratio for death with ribociclib was 0.712 ( P = .00973). An analysis of OS by endocrine partner subgroup showed no significant differences between AIs or tamoxifen.

At the time of the data cutoff, 35% of patients in the ribociclib arm were still on therapy.

The safety and tolerability of the combination were consistent with those previously reported, Dr. Hurvitz said.

“In an era when we are thinking about value in oncology care, a demonstration of a robust sutvival difference I think substantially adds to a value proposition for products like ribociclib that were discussed here,” Dr. Burstein said.

“Hopefully, these data will enable access to this product to more women around the world, particularly in health care systems that assess value rigorously as part of their decisions for national access to drugs,” he added.

The MONALEESA-7 trial is supported by Novartis. Dr. Hurvitz reported travel and accommodation expenses from Novartis. Dr. Burstein reported no relevant disclosures.

SOURCE: Hurvitz SA et al. ASCO 2019. Abstract LBA1008 .

CHICAGO – Adding ribociclib to endocrine therapy significantly improved overall survival of premenopausal women with advanced hormone receptor positive, HER2-negative breast cancer, results of the randomized phase 3 MONALEESA-7 trial showed.

Neil Osterweil/MDedge News

A landmark analysis conducted at 42 months showed that the overall survival rate for women randomized to receive endocrine therapy with either a nonsteroidal aromatase inhibitor (AI) or tamoxifen plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib was 70%, compared with 46% for women randomized to endocrine therapy alone, reported Sara A Hurvitz, MD, of the University of California Los Angeles Jonsson Comprehensive Cancer Center

“This is the first time a statistically significant improvement in overall survival has been observed with a CDK4/6 inhibitor in combination with endocrine therapy in patients with hormone receptor-positive advanced disease,” she said at a briefing prior to her presentation of the data in an oral abstract session at the American Society of Clinical Oncology annual meeting.

“This is an important study, because it shows that the class of drugs, CDK4/6 inhibitors, which we are widely using, has been shown to delay the time to progression, delay the time to need for chemotherapy for advanced breast cancer, and really doubled the effectiveness of endocrine therapy, now also translates into a significant survival benefit for women who ER-positive metastatic breast cancer,” commented Harold J. Burstein, MD, PhD, an ASCO expert from the Dana-Farber Cancer Institute in Boston.

Neil Osterweil/MDedge News

In the trial, 672 pre- or perimenopausal women with HR+/HER2– advanced breast cancer with no prior endocrine therapy for advanced disease and no more than one line of chemotherapy for advanced disease were enrolled. The patients were stratified by the presence of liver/lung metastases, prior chemotherapy, and prior endocrine partner, tamoxifen or nonsteroidal AI, and then randomly assigned to ribociclib 600 mg/day for 3 weeks, followed by 1-week off, plus tamoxifen or AI and goserelin, or the same combination and schedule with placebo.

Of the 672 patients enrolled, a total of 335 patients assigned to ribociclib and 337 assigned to placebo received treatment. The majority of patients – 495 – received an AI, either letrozole (Femara) or anastrozole (Arimidex). Dr. Hurvitz noted that after the initiation of MONALEESA-7, the combination of a CDK4/6 inhibitor and tamoxifen was found to prolong the QT interval and increase risk for cardiac arrhythmias, and is now contraindicated.

As previously reported , results of the primary MONALEESA-7 endpoint of progression-free survival favored the combination, with a median PFS of 23.8 months, compared with 13 months for women treated with endocrine therapy alone. The hazard ratio for progression with the ribociclib-based combination was 0.553 ( P less than .0001), and the treatment benefit of the CDK4/6 inhibitor was seen across all patients subgroups and regardless of the endocrine partner.

At ASCO 2019, Dr. Hurvitz reported on the key secondary endpoint of overall survival. At a median follow-up duration of 34.6 months, with an additional 15 months beyond the initial analysis, the median OS for the ribociclib arm was not reached, compared with 40.9 months in the placebo arm. The hazard ratio for death with ribociclib was 0.712 ( P = .00973). An analysis of OS by endocrine partner subgroup showed no significant differences between AIs or tamoxifen.

At the time of the data cutoff, 35% of patients in the ribociclib arm were still on therapy.

The safety and tolerability of the combination were consistent with those previously reported, Dr. Hurvitz said.

“In an era when we are thinking about value in oncology care, a demonstration of a robust sutvival difference I think substantially adds to a value proposition for products like ribociclib that were discussed here,” Dr. Burstein said.

“Hopefully, these data will enable access to this product to more women around the world, particularly in health care systems that assess value rigorously as part of their decisions for national access to drugs,” he added.

The MONALEESA-7 trial is supported by Novartis. Dr. Hurvitz reported travel and accommodation expenses from Novartis. Dr. Burstein reported no relevant disclosures.

SOURCE: Hurvitz SA et al. ASCO 2019. Abstract LBA1008 .

CHICAGO – Adding ribociclib to endocrine therapy significantly improved overall survival of premenopausal women with advanced hormone receptor positive, HER2-negative breast cancer, results of the randomized phase 3 MONALEESA-7 trial showed.

Neil Osterweil/MDedge News

A landmark analysis conducted at 42 months showed that the overall survival rate for women randomized to receive endocrine therapy with either a nonsteroidal aromatase inhibitor (AI) or tamoxifen plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib was 70%, compared with 46% for women randomized to endocrine therapy alone, reported Sara A Hurvitz, MD, of the University of California Los Angeles Jonsson Comprehensive Cancer Center

“This is the first time a statistically significant improvement in overall survival has been observed with a CDK4/6 inhibitor in combination with endocrine therapy in patients with hormone receptor-positive advanced disease,” she said at a briefing prior to her presentation of the data in an oral abstract session at the American Society of Clinical Oncology annual meeting.

“This is an important study, because it shows that the class of drugs, CDK4/6 inhibitors, which we are widely using, has been shown to delay the time to progression, delay the time to need for chemotherapy for advanced breast cancer, and really doubled the effectiveness of endocrine therapy, now also translates into a significant survival benefit for women who ER-positive metastatic breast cancer,” commented Harold J. Burstein, MD, PhD, an ASCO expert from the Dana-Farber Cancer Institute in Boston.

Neil Osterweil/MDedge News

In the trial, 672 pre- or perimenopausal women with HR+/HER2– advanced breast cancer with no prior endocrine therapy for advanced disease and no more than one line of chemotherapy for advanced disease were enrolled. The patients were stratified by the presence of liver/lung metastases, prior chemotherapy, and prior endocrine partner, tamoxifen or nonsteroidal AI, and then randomly assigned to ribociclib 600 mg/day for 3 weeks, followed by 1-week off, plus tamoxifen or AI and goserelin, or the same combination and schedule with placebo.

Of the 672 patients enrolled, a total of 335 patients assigned to ribociclib and 337 assigned to placebo received treatment. The majority of patients – 495 – received an AI, either letrozole (Femara) or anastrozole (Arimidex). Dr. Hurvitz noted that after the initiation of MONALEESA-7, the combination of a CDK4/6 inhibitor and tamoxifen was found to prolong the QT interval and increase risk for cardiac arrhythmias, and is now contraindicated.

As previously reported , results of the primary MONALEESA-7 endpoint of progression-free survival favored the combination, with a median PFS of 23.8 months, compared with 13 months for women treated with endocrine therapy alone. The hazard ratio for progression with the ribociclib-based combination was 0.553 ( P less than .0001), and the treatment benefit of the CDK4/6 inhibitor was seen across all patients subgroups and regardless of the endocrine partner.

At ASCO 2019, Dr. Hurvitz reported on the key secondary endpoint of overall survival. At a median follow-up duration of 34.6 months, with an additional 15 months beyond the initial analysis, the median OS for the ribociclib arm was not reached, compared with 40.9 months in the placebo arm. The hazard ratio for death with ribociclib was 0.712 ( P = .00973). An analysis of OS by endocrine partner subgroup showed no significant differences between AIs or tamoxifen.

At the time of the data cutoff, 35% of patients in the ribociclib arm were still on therapy.

The safety and tolerability of the combination were consistent with those previously reported, Dr. Hurvitz said.

“In an era when we are thinking about value in oncology care, a demonstration of a robust sutvival difference I think substantially adds to a value proposition for products like ribociclib that were discussed here,” Dr. Burstein said.

“Hopefully, these data will enable access to this product to more women around the world, particularly in health care systems that assess value rigorously as part of their decisions for national access to drugs,” he added.

The MONALEESA-7 trial is supported by Novartis. Dr. Hurvitz reported travel and accommodation expenses from Novartis. Dr. Burstein reported no relevant disclosures.

SOURCE: Hurvitz SA et al. ASCO 2019. Abstract LBA1008 .

CHICAGO – Adding ribociclib to endocrine therapy significantly improved overall survival of premenopausal women with advanced hormone receptor positive, HER2-negative breast cancer, results of the randomized phase 3 MONALEESA-7 trial showed.

A landmark analysis performed at 42 months of follow-up showed that the overall survival (OS) rate for women randomized to receive endocrine therapy with either a nonsteroidal aromatase inhibitor (AI) or tamoxifen plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) was 70%, compared with 46% for women randomized to endocrine therapy plus placebo.

The trial is the first study to evaluate a CDK4/6 inhibitor exclusively in premenopausal women, and the first to show a statistically significant improvement in overall survival with a CDK4/6 inhibitor in combination with endocrine therapy in patients with HR-positive, HER2-negative advanced breast cancer.

In a video interview at the American Society of Clinical Oncology annual meeting, Sara A. Hurvitz, MD, from the University of California Los Angeles Jonsson Comprehensive Cancer Center, describes the significance of the MONALEESA-7 findings and the potential for improving on the study results with other agents or combinations.

The MONALEESA-7 trial is supported by Novartis. Dr. Hurvitz reported travel and accommodation expenses from Novartis.

CHICAGO – Adding ribociclib to endocrine therapy significantly improved overall survival of premenopausal women with advanced hormone receptor positive, HER2-negative breast cancer, results of the randomized phase 3 MONALEESA-7 trial showed.

A landmark analysis performed at 42 months of follow-up showed that the overall survival (OS) rate for women randomized to receive endocrine therapy with either a nonsteroidal aromatase inhibitor (AI) or tamoxifen plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) was 70%, compared with 46% for women randomized to endocrine therapy plus placebo.

The trial is the first study to evaluate a CDK4/6 inhibitor exclusively in premenopausal women, and the first to show a statistically significant improvement in overall survival with a CDK4/6 inhibitor in combination with endocrine therapy in patients with HR-positive, HER2-negative advanced breast cancer.

In a video interview at the American Society of Clinical Oncology annual meeting, Sara A. Hurvitz, MD, from the University of California Los Angeles Jonsson Comprehensive Cancer Center, describes the significance of the MONALEESA-7 findings and the potential for improving on the study results with other agents or combinations.

The MONALEESA-7 trial is supported by Novartis. Dr. Hurvitz reported travel and accommodation expenses from Novartis.

CHICAGO – Adding ribociclib to endocrine therapy significantly improved overall survival of premenopausal women with advanced hormone receptor positive, HER2-negative breast cancer, results of the randomized phase 3 MONALEESA-7 trial showed.

A landmark analysis performed at 42 months of follow-up showed that the overall survival (OS) rate for women randomized to receive endocrine therapy with either a nonsteroidal aromatase inhibitor (AI) or tamoxifen plus the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) was 70%, compared with 46% for women randomized to endocrine therapy plus placebo.

The trial is the first study to evaluate a CDK4/6 inhibitor exclusively in premenopausal women, and the first to show a statistically significant improvement in overall survival with a CDK4/6 inhibitor in combination with endocrine therapy in patients with HR-positive, HER2-negative advanced breast cancer.

In a video interview at the American Society of Clinical Oncology annual meeting, Sara A. Hurvitz, MD, from the University of California Los Angeles Jonsson Comprehensive Cancer Center, describes the significance of the MONALEESA-7 findings and the potential for improving on the study results with other agents or combinations.

The MONALEESA-7 trial is supported by Novartis. Dr. Hurvitz reported travel and accommodation expenses from Novartis.

The Food and Drug Administration has approved the first PI3K inhibitor for the treatment of breast cancer.

The drug, alpelisib (Piqray), was approved for use in combination with fulvestrant for men and postmenopausal women who have hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative, PIK3CA-mutated, advanced or metastatic breast cancer after progression on, or after, an endocrine-based regimen. The approval was announced by the FDA in a statement.

The agency also approved a diagnostic test – the therascreen PIK3CA RGQ PCR Kit – for detecting the PIK3CA mutation. The approval is based on results from the SOLAR-1 trial. In 572 HR-positive, HER2-negative patients with advanced or metastatic breast cancer who progressed after, or during, treatment with an aromatase inhibitor, the addition of alpelisib to fulvestrant significantly improved progression-free survival in patients with PIK3CA mutated tumors.

Median progression-free survival was 5.7 months on fulvestrant plus placebo, versus 11 months with fulvestrant plus alpelisib (hazard ratio for progression or death, 0.65; 95% confidence interval, 0.50-0.85; P less than .001). The results of the trial were recently published in the New England Journal of Medicine (2019 May 16;380[20]:1929-40).

In the FDA statement, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, noted that alpelisib is the “first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer.”

The drug’s application was approved under the Real-Time Oncology Review pilot program, which allows the FDA to begin analyzing efficacy and safety databases before a new drug application is even submitted.

The FDA noted that patients should not start treatment on alpelisib if they have a history of severe skin reactions, such as Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis.

[email protected]

The Food and Drug Administration has approved the first PI3K inhibitor for the treatment of breast cancer.

The drug, alpelisib (Piqray), was approved for use in combination with fulvestrant for men and postmenopausal women who have hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative, PIK3CA-mutated, advanced or metastatic breast cancer after progression on, or after, an endocrine-based regimen. The approval was announced by the FDA in a statement.

The agency also approved a diagnostic test – the therascreen PIK3CA RGQ PCR Kit – for detecting the PIK3CA mutation. The approval is based on results from the SOLAR-1 trial. In 572 HR-positive, HER2-negative patients with advanced or metastatic breast cancer who progressed after, or during, treatment with an aromatase inhibitor, the addition of alpelisib to fulvestrant significantly improved progression-free survival in patients with PIK3CA mutated tumors.

Median progression-free survival was 5.7 months on fulvestrant plus placebo, versus 11 months with fulvestrant plus alpelisib (hazard ratio for progression or death, 0.65; 95% confidence interval, 0.50-0.85; P less than .001). The results of the trial were recently published in the New England Journal of Medicine (2019 May 16;380[20]:1929-40).

In the FDA statement, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, noted that alpelisib is the “first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer.”

The drug’s application was approved under the Real-Time Oncology Review pilot program, which allows the FDA to begin analyzing efficacy and safety databases before a new drug application is even submitted.

The FDA noted that patients should not start treatment on alpelisib if they have a history of severe skin reactions, such as Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis.

[email protected]

The Food and Drug Administration has approved the first PI3K inhibitor for the treatment of breast cancer.

The drug, alpelisib (Piqray), was approved for use in combination with fulvestrant for men and postmenopausal women who have hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative, PIK3CA-mutated, advanced or metastatic breast cancer after progression on, or after, an endocrine-based regimen. The approval was announced by the FDA in a statement.

The agency also approved a diagnostic test – the therascreen PIK3CA RGQ PCR Kit – for detecting the PIK3CA mutation. The approval is based on results from the SOLAR-1 trial. In 572 HR-positive, HER2-negative patients with advanced or metastatic breast cancer who progressed after, or during, treatment with an aromatase inhibitor, the addition of alpelisib to fulvestrant significantly improved progression-free survival in patients with PIK3CA mutated tumors.

Median progression-free survival was 5.7 months on fulvestrant plus placebo, versus 11 months with fulvestrant plus alpelisib (hazard ratio for progression or death, 0.65; 95% confidence interval, 0.50-0.85; P less than .001). The results of the trial were recently published in the New England Journal of Medicine (2019 May 16;380[20]:1929-40).

In the FDA statement, Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, noted that alpelisib is the “first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer.”

The drug’s application was approved under the Real-Time Oncology Review pilot program, which allows the FDA to begin analyzing efficacy and safety databases before a new drug application is even submitted.

The FDA noted that patients should not start treatment on alpelisib if they have a history of severe skin reactions, such as Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis.

[email protected]

Routine use of the Oncotype DX recurrence score to personalize treatment of early breast cancer could reduce the first-year costs of care, according to results of a population-based cohort study.

“Practice changes based on evidence from the TAILORx trial on using tumor genomic profiles to personalize care could result in small decreases in U.S. national cancer care costs in the initial 12 months post breast cancer diagnosis,” Angela Mariotto, PhD, and colleagues concluded in a study published in JNCI: Journal of the National Cancer Institute. “Longer-term studies will be needed to evaluate the true long-term economic impact and nonmonetary benefits of personalized breast cancer care.”

Findings of the landmark TAILORx trial showed that, with use of the 21-gene score, the majority of women who have node-negative, hormone receptor–positive, HER2-negative breast cancers could safely skip adjuvant chemotherapy (N Engl J Med. 2018;379:111-21). But cost impact of its uptake into routine practice is unclear.

Dr. Mariotto, of the National Cancer Institute and her colleagues used data from the Surveillance, Epidemiology and End Results (SEER), SEER-Medicare, and SEER–Genomic Health datasets to assess how expected changes in practice after the trial might affect costs. They estimated Oncotype DX testing and chemotherapy rates and mean initial costs in 2018 dollars in the pre-TAILORx period (2010-2015) and post-TAILORx period (2018), assuming all women in the latter period received the test and score-suggested therapy.

Going from the pretrial period to the posttrial period, Oncotype DX testing costs were projected to increase from $115 million to $231 million, but chemotherapy use was projected to decrease from 25% to 17%. Mean total initial costs of care fell from $2.816 billion in the pretrial period to $2.766 billion in the posttrial period, for a net savings of $49 million (a 1.8% decrease).

Findings were similar in a variety of sensitivity scenarios entailing alternative compliance with testing, score-suggested treatment, and estimation methods. The only exception was the scenario in which all women aged 50 years or younger having a recurrence score of 16-25 opted to receive chemotherapy, wherein initial care costs could increase by $105 million (a 4% increase).

The investigators reported that they had no relevant conflicts of interest. The study was supported by the National Cancer Institute and its Coordinating Center For Clinical Trials; a Lombardi Comprehensive Cancer Center American Cancer Society Young Investigator Award; and the Cancer Prevention Research Fellowship, sponsored by the American Society of Preventive Oncology and Breast Cancer Research Foundation.

SOURCE: Mariotto A et al. J Natl Cancer Inst. 2019 Apr 24. doi: 10.1093/jnci/djz068.

Routine use of the Oncotype DX recurrence score to personalize treatment of early breast cancer could reduce the first-year costs of care, according to results of a population-based cohort study.

“Practice changes based on evidence from the TAILORx trial on using tumor genomic profiles to personalize care could result in small decreases in U.S. national cancer care costs in the initial 12 months post breast cancer diagnosis,” Angela Mariotto, PhD, and colleagues concluded in a study published in JNCI: Journal of the National Cancer Institute. “Longer-term studies will be needed to evaluate the true long-term economic impact and nonmonetary benefits of personalized breast cancer care.”

Findings of the landmark TAILORx trial showed that, with use of the 21-gene score, the majority of women who have node-negative, hormone receptor–positive, HER2-negative breast cancers could safely skip adjuvant chemotherapy (N Engl J Med. 2018;379:111-21). But cost impact of its uptake into routine practice is unclear.

Dr. Mariotto, of the National Cancer Institute and her colleagues used data from the Surveillance, Epidemiology and End Results (SEER), SEER-Medicare, and SEER–Genomic Health datasets to assess how expected changes in practice after the trial might affect costs. They estimated Oncotype DX testing and chemotherapy rates and mean initial costs in 2018 dollars in the pre-TAILORx period (2010-2015) and post-TAILORx period (2018), assuming all women in the latter period received the test and score-suggested therapy.

Going from the pretrial period to the posttrial period, Oncotype DX testing costs were projected to increase from $115 million to $231 million, but chemotherapy use was projected to decrease from 25% to 17%. Mean total initial costs of care fell from $2.816 billion in the pretrial period to $2.766 billion in the posttrial period, for a net savings of $49 million (a 1.8% decrease).

Findings were similar in a variety of sensitivity scenarios entailing alternative compliance with testing, score-suggested treatment, and estimation methods. The only exception was the scenario in which all women aged 50 years or younger having a recurrence score of 16-25 opted to receive chemotherapy, wherein initial care costs could increase by $105 million (a 4% increase).

The investigators reported that they had no relevant conflicts of interest. The study was supported by the National Cancer Institute and its Coordinating Center For Clinical Trials; a Lombardi Comprehensive Cancer Center American Cancer Society Young Investigator Award; and the Cancer Prevention Research Fellowship, sponsored by the American Society of Preventive Oncology and Breast Cancer Research Foundation.

SOURCE: Mariotto A et al. J Natl Cancer Inst. 2019 Apr 24. doi: 10.1093/jnci/djz068.

Routine use of the Oncotype DX recurrence score to personalize treatment of early breast cancer could reduce the first-year costs of care, according to results of a population-based cohort study.

“Practice changes based on evidence from the TAILORx trial on using tumor genomic profiles to personalize care could result in small decreases in U.S. national cancer care costs in the initial 12 months post breast cancer diagnosis,” Angela Mariotto, PhD, and colleagues concluded in a study published in JNCI: Journal of the National Cancer Institute. “Longer-term studies will be needed to evaluate the true long-term economic impact and nonmonetary benefits of personalized breast cancer care.”

Findings of the landmark TAILORx trial showed that, with use of the 21-gene score, the majority of women who have node-negative, hormone receptor–positive, HER2-negative breast cancers could safely skip adjuvant chemotherapy (N Engl J Med. 2018;379:111-21). But cost impact of its uptake into routine practice is unclear.

Dr. Mariotto, of the National Cancer Institute and her colleagues used data from the Surveillance, Epidemiology and End Results (SEER), SEER-Medicare, and SEER–Genomic Health datasets to assess how expected changes in practice after the trial might affect costs. They estimated Oncotype DX testing and chemotherapy rates and mean initial costs in 2018 dollars in the pre-TAILORx period (2010-2015) and post-TAILORx period (2018), assuming all women in the latter period received the test and score-suggested therapy.

Going from the pretrial period to the posttrial period, Oncotype DX testing costs were projected to increase from $115 million to $231 million, but chemotherapy use was projected to decrease from 25% to 17%. Mean total initial costs of care fell from $2.816 billion in the pretrial period to $2.766 billion in the posttrial period, for a net savings of $49 million (a 1.8% decrease).

Findings were similar in a variety of sensitivity scenarios entailing alternative compliance with testing, score-suggested treatment, and estimation methods. The only exception was the scenario in which all women aged 50 years or younger having a recurrence score of 16-25 opted to receive chemotherapy, wherein initial care costs could increase by $105 million (a 4% increase).

The investigators reported that they had no relevant conflicts of interest. The study was supported by the National Cancer Institute and its Coordinating Center For Clinical Trials; a Lombardi Comprehensive Cancer Center American Cancer Society Young Investigator Award; and the Cancer Prevention Research Fellowship, sponsored by the American Society of Preventive Oncology and Breast Cancer Research Foundation.

SOURCE: Mariotto A et al. J Natl Cancer Inst. 2019 Apr 24. doi: 10.1093/jnci/djz068.

A balanced, low-fat diet was associated with a lower risk of death from breast cancer in a large cohort of postmenopausal women who had no previous history of breast cancer.

Researchers studied nearly 49,000 postmenopausal women and found a 21% lower risk of death from breast cancer among women who followed the balanced, low-fat diet, compared with women who followed their normal diet.

This research is scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, Calif., discussed the research during a press briefing in advance of the meeting.
 

About the study

The research is part of the Woman’s Health Initiative (NCT00000611), which is focused on investigating methods for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.

This trial enrolled 48,835 postmenopausal women, ages 50-79 years, with no history of breast cancer and normal mammograms at enrollment. From 1993 to 1998, the women were randomized to the study diet (n = 19,541) or their normal diet (n = 29,294).

With the normal diet, fat accounted for 32% or more of subjects’ daily calories. With the study diet, the goal was to reduce fat consumption to 20% or less of caloric intake. The study diet also required at least one daily serving of vegetables, fruits, and grains.

Dr. Chlebowski said the study diet is similar to DASH (Dietary Approaches to Stop Hypertension), but is slightly more focused on lowering fat intake.
 

Diet adherence

Subjects followed the study diet for a median of 8.5 years, and the median cumulative follow-up was 19.6 years.

Dr. Chlebowski noted that most women on the study diet were not able to reduce their daily fat consumption to the 20% goal. They did reduce fat consumption to 24.5% overall, which increased to 29% at the end of the intervention.

In the study-diet group, there was an average weight loss of 3%, significantly different from that of the normal-diet group (P less than .001).

Dr. Chlebowski said the weight loss indicates that subjects did adhere to the study diet, at least in part, as there was no change in physical activity among study participants. Furthermore, the researchers have evidence after 1 year that suggests subjects were incorporating more fruits and vegetables into their diets.
 

Breast cancer and death

At a median follow-up of 19.6 years, there were 3,374 cases of breast cancer, 1,011 deaths, and 383 deaths attributed to breast cancer.

The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group. The hazard ratio was 0.79 (95% confidence interval, 0.64-0.97; P = .025).

The risk of death (from any cause) after breast cancer was significantly lower in the study diet group as well, with a hazard ratio of 0.85 (95% confidence interval, 0.74-0.96; P = .01).

“Adoption of a low-fat dietary pattern reduces the risk of death from breast cancer in postmenopausal women,” Dr. Chlebowski said. “To our review, this is the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer.”

Dr. Chlebowski noted that the researchers have blood samples from all subjects enrolled in this study. The researchers plan to analyze those samples to further explore how the study diet affected the women and determine which components of the diet account for which effects.

The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.

SOURCE: Chlebowski R. et al. ASCO 2019. Abstract 520.

A balanced, low-fat diet was associated with a lower risk of death from breast cancer in a large cohort of postmenopausal women who had no previous history of breast cancer.

Researchers studied nearly 49,000 postmenopausal women and found a 21% lower risk of death from breast cancer among women who followed the balanced, low-fat diet, compared with women who followed their normal diet.

This research is scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, Calif., discussed the research during a press briefing in advance of the meeting.
 

About the study

The research is part of the Woman’s Health Initiative (NCT00000611), which is focused on investigating methods for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.

This trial enrolled 48,835 postmenopausal women, ages 50-79 years, with no history of breast cancer and normal mammograms at enrollment. From 1993 to 1998, the women were randomized to the study diet (n = 19,541) or their normal diet (n = 29,294).

With the normal diet, fat accounted for 32% or more of subjects’ daily calories. With the study diet, the goal was to reduce fat consumption to 20% or less of caloric intake. The study diet also required at least one daily serving of vegetables, fruits, and grains.

Dr. Chlebowski said the study diet is similar to DASH (Dietary Approaches to Stop Hypertension), but is slightly more focused on lowering fat intake.
 

Diet adherence

Subjects followed the study diet for a median of 8.5 years, and the median cumulative follow-up was 19.6 years.

Dr. Chlebowski noted that most women on the study diet were not able to reduce their daily fat consumption to the 20% goal. They did reduce fat consumption to 24.5% overall, which increased to 29% at the end of the intervention.

In the study-diet group, there was an average weight loss of 3%, significantly different from that of the normal-diet group (P less than .001).

Dr. Chlebowski said the weight loss indicates that subjects did adhere to the study diet, at least in part, as there was no change in physical activity among study participants. Furthermore, the researchers have evidence after 1 year that suggests subjects were incorporating more fruits and vegetables into their diets.
 

Breast cancer and death

At a median follow-up of 19.6 years, there were 3,374 cases of breast cancer, 1,011 deaths, and 383 deaths attributed to breast cancer.

The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group. The hazard ratio was 0.79 (95% confidence interval, 0.64-0.97; P = .025).

The risk of death (from any cause) after breast cancer was significantly lower in the study diet group as well, with a hazard ratio of 0.85 (95% confidence interval, 0.74-0.96; P = .01).

“Adoption of a low-fat dietary pattern reduces the risk of death from breast cancer in postmenopausal women,” Dr. Chlebowski said. “To our review, this is the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer.”

Dr. Chlebowski noted that the researchers have blood samples from all subjects enrolled in this study. The researchers plan to analyze those samples to further explore how the study diet affected the women and determine which components of the diet account for which effects.

The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.

SOURCE: Chlebowski R. et al. ASCO 2019. Abstract 520.

A balanced, low-fat diet was associated with a lower risk of death from breast cancer in a large cohort of postmenopausal women who had no previous history of breast cancer.

Researchers studied nearly 49,000 postmenopausal women and found a 21% lower risk of death from breast cancer among women who followed the balanced, low-fat diet, compared with women who followed their normal diet.

This research is scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Rowan Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center in Torrance, Calif., discussed the research during a press briefing in advance of the meeting.
 

About the study

The research is part of the Woman’s Health Initiative (NCT00000611), which is focused on investigating methods for preventing heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal women.

This trial enrolled 48,835 postmenopausal women, ages 50-79 years, with no history of breast cancer and normal mammograms at enrollment. From 1993 to 1998, the women were randomized to the study diet (n = 19,541) or their normal diet (n = 29,294).

With the normal diet, fat accounted for 32% or more of subjects’ daily calories. With the study diet, the goal was to reduce fat consumption to 20% or less of caloric intake. The study diet also required at least one daily serving of vegetables, fruits, and grains.

Dr. Chlebowski said the study diet is similar to DASH (Dietary Approaches to Stop Hypertension), but is slightly more focused on lowering fat intake.
 

Diet adherence

Subjects followed the study diet for a median of 8.5 years, and the median cumulative follow-up was 19.6 years.

Dr. Chlebowski noted that most women on the study diet were not able to reduce their daily fat consumption to the 20% goal. They did reduce fat consumption to 24.5% overall, which increased to 29% at the end of the intervention.

In the study-diet group, there was an average weight loss of 3%, significantly different from that of the normal-diet group (P less than .001).

Dr. Chlebowski said the weight loss indicates that subjects did adhere to the study diet, at least in part, as there was no change in physical activity among study participants. Furthermore, the researchers have evidence after 1 year that suggests subjects were incorporating more fruits and vegetables into their diets.
 

Breast cancer and death

At a median follow-up of 19.6 years, there were 3,374 cases of breast cancer, 1,011 deaths, and 383 deaths attributed to breast cancer.

The risk of death from breast cancer was significantly lower in the study-diet group than in the normal-diet group. The hazard ratio was 0.79 (95% confidence interval, 0.64-0.97; P = .025).

The risk of death (from any cause) after breast cancer was significantly lower in the study diet group as well, with a hazard ratio of 0.85 (95% confidence interval, 0.74-0.96; P = .01).

“Adoption of a low-fat dietary pattern reduces the risk of death from breast cancer in postmenopausal women,” Dr. Chlebowski said. “To our review, this is the only study providing randomized clinical trial evidence that an intervention can reduce a woman’s risk of dying from breast cancer.”

Dr. Chlebowski noted that the researchers have blood samples from all subjects enrolled in this study. The researchers plan to analyze those samples to further explore how the study diet affected the women and determine which components of the diet account for which effects.

The National Institutes of Health funded the study. The researchers disclosed relationships with Novartis, Pfizer, Amgen, AstraZeneca, Immunomedics, Metastat, Bayer, and Genentech/Roche.

SOURCE: Chlebowski R. et al. ASCO 2019. Abstract 520.

Patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer who had previously undergone endocrine therapy experienced longer progression-free survival when receiving alpelisib and fulvestrant, compared with placebo and fulvestrant (11.0 vs. 5.7 months; hazard ratio, 0.65; 95% confidence interval, 0.50-0.85; P less than .001), according to a randomized, phase 3 trial published in the New England Journal of Medicine (2019 May 15. doi: 10.1056/NEJMoa1813904).

We first reported on the results of this trial when they were presented at the European Society for Medical Oncology Congress. Find our coverage at the link below.

Patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer who had previously undergone endocrine therapy experienced longer progression-free survival when receiving alpelisib and fulvestrant, compared with placebo and fulvestrant (11.0 vs. 5.7 months; hazard ratio, 0.65; 95% confidence interval, 0.50-0.85; P less than .001), according to a randomized, phase 3 trial published in the New England Journal of Medicine (2019 May 15. doi: 10.1056/NEJMoa1813904).

We first reported on the results of this trial when they were presented at the European Society for Medical Oncology Congress. Find our coverage at the link below.

Patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer who had previously undergone endocrine therapy experienced longer progression-free survival when receiving alpelisib and fulvestrant, compared with placebo and fulvestrant (11.0 vs. 5.7 months; hazard ratio, 0.65; 95% confidence interval, 0.50-0.85; P less than .001), according to a randomized, phase 3 trial published in the New England Journal of Medicine (2019 May 15. doi: 10.1056/NEJMoa1813904).

We first reported on the results of this trial when they were presented at the European Society for Medical Oncology Congress. Find our coverage at the link below.

ATLANTA – Adding intratumoral talimogene laherparepvec (TVEC) to neoadjuvant chemotherapy appears to improve response rates in patients with nonmetastatic triple-negative breast cancer, according to findings from a phase 1 trial.

The pathologic complete response rate (pCR) in nine patients aged 18-70 years with stage T2-T3NO-2 disease who were enrolled in the single-center trial was 55%, whereas the expected rate with neoadjuvant chemotherapy alone was 30%, Hatem Soliman, MD, reported at the annual meeting of the American Association for Cancer Research.

“Even in the patients with residual disease, they had almost complete obliteration of their tumors, as well,” said Dr. Soliman of Moffitt Cancer Center, Tampa, Fla., adding that preliminary analyses of T cell subtypes indicated that CD45RO+ cells, which are associated with activated memory effector phenotype cells, were found in higher percentages in tumor specimens from patients who had pCR vs. those who did not.

“This could be an emerging marker that could be associated with pCR from TVEC,” he said, stressing, however, that “this is preliminary data [that] needs to be borne out in subsequent studies.”

Of the nine participants, six had stage II disease and three had stage III disease, and tumor size was greater than 5 cm in 2 patients, and 2-5 cm in 7 patients. Three received 10⁶ plaque-forming units (PFUs) x 5 injections (dose level 1), and 6 received 10⁶ PFUs for the first injection then 10⁸ PFUs for 4 additional injections. Patients also received neoadjuvant paclitaxel followed by doxorubicin/cyclophosphamide chemotherapy.

They then went on to surgery and were evaluated for pCR.

No dose-limiting toxicities occurred, therefore the maximum-tolerated dose was dose level 2, Dr. Soliman noted.

The most common toxicities due to TVEC were fevers, chills, and injection site reactions, and “these are considered expected side effects of TVEC administration and were manageable,” he said.

Two serious adverse events occurred in the trial: a pulmonary embolism and a postoperative case of severe bradycardia thought to be a vasovagal episode; there were no deaths or any sequelae from these adverse events and they completely resolved.

One latent genital wild type herpes simplex 1 virus (HSV1) reactivation event occurred and was treated with a topical agent.


Early-stage triple-negative breast cancer is associated with a higher risk of early relapse, but attaining a pCR after neoadjuvant chemotherapy is associated with improved prognosis, Dr. Soliman said.

“Historically, standard regimens used for triple-negative breast cancer include an anthracycline and a taxane, and the rates of pCR in those patients hover around 30%,” he said. “Others have looked at the relationship of increased tumor infiltrating lymphocytes (TILs] in triple-negative breast cancers and other breast cancers, and found that those tumors that did have a higher de novo TIL infiltrate, either at the beginning of treatment or acquired during treatment, seemed to have a higher rate of pCR and also seemed to have improved prognosis.”

This suggested that these TIL infiltrates may be both a predictive and prognostic biologic marker for the biology of the disease, he noted.

Further, promising prior research on the role of oncolytic viruses as a potential treatment modality for cancer led to interest in their use during neoadjuvant chemotherapy “with the idea that we could potentially improve pathologic complete response rates both through direct tumor cell lysis of treated tumors, but also through recruitment of a robust antitumor immune response caused by the viruses’ mechanism of action,” he said, adding that “this could be beneficial, particularly in those immunologically ‘cold’ tumors.”

This led to the incorporation of TVEC, a genetically engineered oncolytic HSV1 currently approved for the treatment of melanoma, in this neoadjuvant trial. TVEC preferentially lyses tumor cells over normal tissue to release tumor associated antigens, produces granulocyte-macrophage colony-stimulating factor to activate dendritic cells, and stimulates T cells to provoke an adaptive immune response, he explained.

“[This] then can not only potentially attack tumor cells at the primary site, but then may potentially spread around the body to improve host surveillance and try to eradicate micrometastatic disease, as well,” he said.

The current findings show that adding TVEC to neoadjuvant chemotherapy is feasible at the full Food and Drug Administration–approved dose and has manageable toxicity, he concluded, noting that “a phase 2 single-arm trial of this regimen is ongoing, and we are actively accruing patients to further evaluate the efficacy signal and formally test the hypothesis along with immune correlates.”

Dr. Soliman reported relationships with Eli Lilly, Pfizer, Celgene, AstraZeneca, PUMA, Novartis, Eisai, and Amgen.

SOURCE: Soliman H et al. AACR 2019, Abstract CT040.

ATLANTA – Adding intratumoral talimogene laherparepvec (TVEC) to neoadjuvant chemotherapy appears to improve response rates in patients with nonmetastatic triple-negative breast cancer, according to findings from a phase 1 trial.

The pathologic complete response rate (pCR) in nine patients aged 18-70 years with stage T2-T3NO-2 disease who were enrolled in the single-center trial was 55%, whereas the expected rate with neoadjuvant chemotherapy alone was 30%, Hatem Soliman, MD, reported at the annual meeting of the American Association for Cancer Research.

“Even in the patients with residual disease, they had almost complete obliteration of their tumors, as well,” said Dr. Soliman of Moffitt Cancer Center, Tampa, Fla., adding that preliminary analyses of T cell subtypes indicated that CD45RO+ cells, which are associated with activated memory effector phenotype cells, were found in higher percentages in tumor specimens from patients who had pCR vs. those who did not.

“This could be an emerging marker that could be associated with pCR from TVEC,” he said, stressing, however, that “this is preliminary data [that] needs to be borne out in subsequent studies.”

Of the nine participants, six had stage II disease and three had stage III disease, and tumor size was greater than 5 cm in 2 patients, and 2-5 cm in 7 patients. Three received 10⁶ plaque-forming units (PFUs) x 5 injections (dose level 1), and 6 received 10⁶ PFUs for the first injection then 10⁸ PFUs for 4 additional injections. Patients also received neoadjuvant paclitaxel followed by doxorubicin/cyclophosphamide chemotherapy.

They then went on to surgery and were evaluated for pCR.

No dose-limiting toxicities occurred, therefore the maximum-tolerated dose was dose level 2, Dr. Soliman noted.

The most common toxicities due to TVEC were fevers, chills, and injection site reactions, and “these are considered expected side effects of TVEC administration and were manageable,” he said.

Two serious adverse events occurred in the trial: a pulmonary embolism and a postoperative case of severe bradycardia thought to be a vasovagal episode; there were no deaths or any sequelae from these adverse events and they completely resolved.

One latent genital wild type herpes simplex 1 virus (HSV1) reactivation event occurred and was treated with a topical agent.


Early-stage triple-negative breast cancer is associated with a higher risk of early relapse, but attaining a pCR after neoadjuvant chemotherapy is associated with improved prognosis, Dr. Soliman said.

“Historically, standard regimens used for triple-negative breast cancer include an anthracycline and a taxane, and the rates of pCR in those patients hover around 30%,” he said. “Others have looked at the relationship of increased tumor infiltrating lymphocytes (TILs] in triple-negative breast cancers and other breast cancers, and found that those tumors that did have a higher de novo TIL infiltrate, either at the beginning of treatment or acquired during treatment, seemed to have a higher rate of pCR and also seemed to have improved prognosis.”

This suggested that these TIL infiltrates may be both a predictive and prognostic biologic marker for the biology of the disease, he noted.

Further, promising prior research on the role of oncolytic viruses as a potential treatment modality for cancer led to interest in their use during neoadjuvant chemotherapy “with the idea that we could potentially improve pathologic complete response rates both through direct tumor cell lysis of treated tumors, but also through recruitment of a robust antitumor immune response caused by the viruses’ mechanism of action,” he said, adding that “this could be beneficial, particularly in those immunologically ‘cold’ tumors.”

This led to the incorporation of TVEC, a genetically engineered oncolytic HSV1 currently approved for the treatment of melanoma, in this neoadjuvant trial. TVEC preferentially lyses tumor cells over normal tissue to release tumor associated antigens, produces granulocyte-macrophage colony-stimulating factor to activate dendritic cells, and stimulates T cells to provoke an adaptive immune response, he explained.

“[This] then can not only potentially attack tumor cells at the primary site, but then may potentially spread around the body to improve host surveillance and try to eradicate micrometastatic disease, as well,” he said.

The current findings show that adding TVEC to neoadjuvant chemotherapy is feasible at the full Food and Drug Administration–approved dose and has manageable toxicity, he concluded, noting that “a phase 2 single-arm trial of this regimen is ongoing, and we are actively accruing patients to further evaluate the efficacy signal and formally test the hypothesis along with immune correlates.”

Dr. Soliman reported relationships with Eli Lilly, Pfizer, Celgene, AstraZeneca, PUMA, Novartis, Eisai, and Amgen.

SOURCE: Soliman H et al. AACR 2019, Abstract CT040.

ATLANTA – Adding intratumoral talimogene laherparepvec (TVEC) to neoadjuvant chemotherapy appears to improve response rates in patients with nonmetastatic triple-negative breast cancer, according to findings from a phase 1 trial.

The pathologic complete response rate (pCR) in nine patients aged 18-70 years with stage T2-T3NO-2 disease who were enrolled in the single-center trial was 55%, whereas the expected rate with neoadjuvant chemotherapy alone was 30%, Hatem Soliman, MD, reported at the annual meeting of the American Association for Cancer Research.

“Even in the patients with residual disease, they had almost complete obliteration of their tumors, as well,” said Dr. Soliman of Moffitt Cancer Center, Tampa, Fla., adding that preliminary analyses of T cell subtypes indicated that CD45RO+ cells, which are associated with activated memory effector phenotype cells, were found in higher percentages in tumor specimens from patients who had pCR vs. those who did not.

“This could be an emerging marker that could be associated with pCR from TVEC,” he said, stressing, however, that “this is preliminary data [that] needs to be borne out in subsequent studies.”

Of the nine participants, six had stage II disease and three had stage III disease, and tumor size was greater than 5 cm in 2 patients, and 2-5 cm in 7 patients. Three received 10⁶ plaque-forming units (PFUs) x 5 injections (dose level 1), and 6 received 10⁶ PFUs for the first injection then 10⁸ PFUs for 4 additional injections. Patients also received neoadjuvant paclitaxel followed by doxorubicin/cyclophosphamide chemotherapy.

They then went on to surgery and were evaluated for pCR.

No dose-limiting toxicities occurred, therefore the maximum-tolerated dose was dose level 2, Dr. Soliman noted.

The most common toxicities due to TVEC were fevers, chills, and injection site reactions, and “these are considered expected side effects of TVEC administration and were manageable,” he said.

Two serious adverse events occurred in the trial: a pulmonary embolism and a postoperative case of severe bradycardia thought to be a vasovagal episode; there were no deaths or any sequelae from these adverse events and they completely resolved.

One latent genital wild type herpes simplex 1 virus (HSV1) reactivation event occurred and was treated with a topical agent.


Early-stage triple-negative breast cancer is associated with a higher risk of early relapse, but attaining a pCR after neoadjuvant chemotherapy is associated with improved prognosis, Dr. Soliman said.

“Historically, standard regimens used for triple-negative breast cancer include an anthracycline and a taxane, and the rates of pCR in those patients hover around 30%,” he said. “Others have looked at the relationship of increased tumor infiltrating lymphocytes (TILs] in triple-negative breast cancers and other breast cancers, and found that those tumors that did have a higher de novo TIL infiltrate, either at the beginning of treatment or acquired during treatment, seemed to have a higher rate of pCR and also seemed to have improved prognosis.”

This suggested that these TIL infiltrates may be both a predictive and prognostic biologic marker for the biology of the disease, he noted.

Further, promising prior research on the role of oncolytic viruses as a potential treatment modality for cancer led to interest in their use during neoadjuvant chemotherapy “with the idea that we could potentially improve pathologic complete response rates both through direct tumor cell lysis of treated tumors, but also through recruitment of a robust antitumor immune response caused by the viruses’ mechanism of action,” he said, adding that “this could be beneficial, particularly in those immunologically ‘cold’ tumors.”

This led to the incorporation of TVEC, a genetically engineered oncolytic HSV1 currently approved for the treatment of melanoma, in this neoadjuvant trial. TVEC preferentially lyses tumor cells over normal tissue to release tumor associated antigens, produces granulocyte-macrophage colony-stimulating factor to activate dendritic cells, and stimulates T cells to provoke an adaptive immune response, he explained.

“[This] then can not only potentially attack tumor cells at the primary site, but then may potentially spread around the body to improve host surveillance and try to eradicate micrometastatic disease, as well,” he said.

The current findings show that adding TVEC to neoadjuvant chemotherapy is feasible at the full Food and Drug Administration–approved dose and has manageable toxicity, he concluded, noting that “a phase 2 single-arm trial of this regimen is ongoing, and we are actively accruing patients to further evaluate the efficacy signal and formally test the hypothesis along with immune correlates.”

Dr. Soliman reported relationships with Eli Lilly, Pfizer, Celgene, AstraZeneca, PUMA, Novartis, Eisai, and Amgen.

SOURCE: Soliman H et al. AACR 2019, Abstract CT040.

Patients with relapsing multiple sclerosis who received 75 mg of the Bruton’s tyrosine kinase inhibitor evobrutinib once daily had significantly fewer enhancing lesions from 12 to 24 weeks than did those who received placebo. However, there was no difference between the 25-mg once daily, 75-mg once daily, 75-mg twice daily, and placebo-treated groups in Expanded Disability Status Scale scores, according to a double-blind, randomized, phase 2 trial published in the New England Journal of Medicine (2019 May 10. doi: 10.1056/NEJMoa1901981).

We first reported on the results of this trial when they were presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Find our coverage at the link below.

[email protected]

Patients with relapsing multiple sclerosis who received 75 mg of the Bruton’s tyrosine kinase inhibitor evobrutinib once daily had significantly fewer enhancing lesions from 12 to 24 weeks than did those who received placebo. However, there was no difference between the 25-mg once daily, 75-mg once daily, 75-mg twice daily, and placebo-treated groups in Expanded Disability Status Scale scores, according to a double-blind, randomized, phase 2 trial published in the New England Journal of Medicine (2019 May 10. doi: 10.1056/NEJMoa1901981).

We first reported on the results of this trial when they were presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Find our coverage at the link below.

[email protected]

Patients with relapsing multiple sclerosis who received 75 mg of the Bruton’s tyrosine kinase inhibitor evobrutinib once daily had significantly fewer enhancing lesions from 12 to 24 weeks than did those who received placebo. However, there was no difference between the 25-mg once daily, 75-mg once daily, 75-mg twice daily, and placebo-treated groups in Expanded Disability Status Scale scores, according to a double-blind, randomized, phase 2 trial published in the New England Journal of Medicine (2019 May 10. doi: 10.1056/NEJMoa1901981).

We first reported on the results of this trial when they were presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Find our coverage at the link below.

[email protected]

We interviewed Dr. Stephen Krieger to discuss his research in the implementation of the topographical model of Multiple Sclerosis.

What is the concept behind the topographical model of multiple sclerosis (MS)?

DR. KRIEGER: MS is an incredibly heterogeneous, and in many ways, unpredictable disease. Some people with MS will have a relapsing course, others will take a progressive course of disease, and many will have a disease course that spans both a relapsing phase and a progressive phase.

We have traditionally divided MS into phenotypes like relapsing-remitting MS (RRMS), secondary-progressive MS (SPMS), or primary-progressive MS (PPMS), and these phenotypes have been foundational in our field and used to define clinical trial cohorts and outcomes. They also have been used for the approval of our medicines. In practice, however, it sometimes can be difficult to know precisely what kind of MS, what phenotypes of MS, that an individual patient has.

The topographical model, which was proposed four years ago, tries to unify our concepts of MS in a way that spans across those phenotypes and animates the disease course in a more dynamic way to bridge from one phenotype to another.

As an individual patient, for example, develops clinically isolated syndrome (CIS) or first attack, and then RRMS, and then later SPMS, that gets depicted in a dynamic visualization through the topographical model. The model also makes use of the idea that where an MS lesion is in the central nervous system (CNS) defines the clinical symptoms that it causes.

This is something that we have long known, and the art of localization in neurology has existed for at least a couple hundred years. But we have not used that in the way we have depicted MS clinical course in recent decades. The topographical model tries to bring this idea of mapping an individual patient’s disease topography back into the clinical picture.

 In the topographical model, the lesions are shown as different topographical peaks, via the hills and valleys of areas of MS damage across different regions of the CNS [image]. They are compensated for by reserve, by the ability that the nervous system has to compensate and to keep a disease process from crossing the clinical threshold and causing symptoms.  What the topographical model displays is that  patients with MS lose reserve as time passes.

We know that there is brain atrophy, brain stem atrophy, spinal cord atrophy, and retinal nerve fiber layer thinning in this disease. The topographical model takes the concept that MS causes a loss of tissue across the CNS and applies it to where the lesions are in the CNS. The coming together of those two things brings about the clinical picture unmasking the deficit from those lesions over time. The short version is a depiction of disease course in MS. The way it looks has been likened to a leaking swimming pool, where there is a shallow end and a deep end, and as reserve drains over time more and more of that subclinical disease becomes unmasked.

In the Laitman article (2018), you applied the model to real patients. What were the main findings from that study?

DR. KRIEGER: Until now, the topographical model has been conceptual with a visual depiction, and I think it has been important as an educational tool and an aid to help shape our thinking about MS in a unified way.

The Laitman et al research, is the first time we have applied the concepts of the model to individual patients to confirm whether we could map individual patients’ MS histories in the topographical model and see if we could depict their clinical course this way. We found that we could.

One of the most important points that the topographical model makes is the idea that as progression occurs and reserve is lost, there is an unmasking of underlying disease. Meaning, all of the signs and symptoms that a patient has had during their relapse when they were accumulating lesions should be re-revealed or recapitulated when reserve is lost and progression occurs.

To confirm this, we mapped ten patients in the topographical model. We characterized their signs and symptoms of relapses during the relapsing phase and we found that the vast majority of these symptoms had redeclared themselves at the time that these patients developed SPMS. Furthermore,  those symptoms were continuing to worsen in their pattern; that is in the pattern of their disease topography as the years have continued to pass since they developed SPMS.

This was the first empirical study in real patients to show that the principles of the topographical model held true. This recapitulation hypothesis of symptoms in progressive disease was borne out, and that can help to lay the groundwork for future empirical studies to see how this model can be used as a predictive tool.

How does this new theory of MS disease progression better inform treatment decisions than the disease course theories that currently exist?

DR. KRIEGER: We have had the clinical phenotypes for 20 years and it has been very helpful to us in the development of treatments that we have shown are effective for RRMS and in more recent years for PPMS. What we don’t really have is a way of personalizing and predicting the individual person’s disease trajectory.

Although we have prognostic factors that we know are important, such as age and MRI disease burden, there is still great uncertainty of the clinical course in the individual patient. If the topographical model can be further empirically validated using real world data, that could help us to predict what is going to happen to an individual patient. That can help us to make better treatment decisions for them because it could inform our treatment decisions in a more personalized way.

Is there any other recent research that supports these concepts?

DR. KRIEGER: We talk a lot about the need for biomarkers in MS to help us predict disease course and the topographical model makes the case that lesion location is a crucial biomarker. That is, the patient that has lesions in the spinal cord and the brain stem is more likely to have progressive signs and symptoms referable to those lesions.

A separate piece of work recently done by Keegan and colleagues that was published in Multiple Sclerosis Journal, looked at their own cohort of patients that had at least one critically located lesion, typically in the high cervical spinal cord or the lower brain stem, as being the crucial driver of the development of motor dysfunction and progressive disability.

In an editorial I wrote with my colleague, Fred Lublin, called “Location, location, location,” we point out that this is in some ways the best data in support of the concept of the topographical model that I have seen. It outlines a framework or a methodology where the importance of lesion location in defining the clinical picture and the risk of progression for an individual patient can be studied.

We interviewed Dr. Stephen Krieger to discuss his research in the implementation of the topographical model of Multiple Sclerosis.

What is the concept behind the topographical model of multiple sclerosis (MS)?

DR. KRIEGER: MS is an incredibly heterogeneous, and in many ways, unpredictable disease. Some people with MS will have a relapsing course, others will take a progressive course of disease, and many will have a disease course that spans both a relapsing phase and a progressive phase.

We have traditionally divided MS into phenotypes like relapsing-remitting MS (RRMS), secondary-progressive MS (SPMS), or primary-progressive MS (PPMS), and these phenotypes have been foundational in our field and used to define clinical trial cohorts and outcomes. They also have been used for the approval of our medicines. In practice, however, it sometimes can be difficult to know precisely what kind of MS, what phenotypes of MS, that an individual patient has.

The topographical model, which was proposed four years ago, tries to unify our concepts of MS in a way that spans across those phenotypes and animates the disease course in a more dynamic way to bridge from one phenotype to another.

As an individual patient, for example, develops clinically isolated syndrome (CIS) or first attack, and then RRMS, and then later SPMS, that gets depicted in a dynamic visualization through the topographical model. The model also makes use of the idea that where an MS lesion is in the central nervous system (CNS) defines the clinical symptoms that it causes.

This is something that we have long known, and the art of localization in neurology has existed for at least a couple hundred years. But we have not used that in the way we have depicted MS clinical course in recent decades. The topographical model tries to bring this idea of mapping an individual patient’s disease topography back into the clinical picture.

 In the topographical model, the lesions are shown as different topographical peaks, via the hills and valleys of areas of MS damage across different regions of the CNS [image]. They are compensated for by reserve, by the ability that the nervous system has to compensate and to keep a disease process from crossing the clinical threshold and causing symptoms.  What the topographical model displays is that  patients with MS lose reserve as time passes.

We know that there is brain atrophy, brain stem atrophy, spinal cord atrophy, and retinal nerve fiber layer thinning in this disease. The topographical model takes the concept that MS causes a loss of tissue across the CNS and applies it to where the lesions are in the CNS. The coming together of those two things brings about the clinical picture unmasking the deficit from those lesions over time. The short version is a depiction of disease course in MS. The way it looks has been likened to a leaking swimming pool, where there is a shallow end and a deep end, and as reserve drains over time more and more of that subclinical disease becomes unmasked.

In the Laitman article (2018), you applied the model to real patients. What were the main findings from that study?

DR. KRIEGER: Until now, the topographical model has been conceptual with a visual depiction, and I think it has been important as an educational tool and an aid to help shape our thinking about MS in a unified way.

The Laitman et al research, is the first time we have applied the concepts of the model to individual patients to confirm whether we could map individual patients’ MS histories in the topographical model and see if we could depict their clinical course this way. We found that we could.

One of the most important points that the topographical model makes is the idea that as progression occurs and reserve is lost, there is an unmasking of underlying disease. Meaning, all of the signs and symptoms that a patient has had during their relapse when they were accumulating lesions should be re-revealed or recapitulated when reserve is lost and progression occurs.

To confirm this, we mapped ten patients in the topographical model. We characterized their signs and symptoms of relapses during the relapsing phase and we found that the vast majority of these symptoms had redeclared themselves at the time that these patients developed SPMS. Furthermore,  those symptoms were continuing to worsen in their pattern; that is in the pattern of their disease topography as the years have continued to pass since they developed SPMS.

This was the first empirical study in real patients to show that the principles of the topographical model held true. This recapitulation hypothesis of symptoms in progressive disease was borne out, and that can help to lay the groundwork for future empirical studies to see how this model can be used as a predictive tool.

How does this new theory of MS disease progression better inform treatment decisions than the disease course theories that currently exist?

DR. KRIEGER: We have had the clinical phenotypes for 20 years and it has been very helpful to us in the development of treatments that we have shown are effective for RRMS and in more recent years for PPMS. What we don’t really have is a way of personalizing and predicting the individual person’s disease trajectory.

Although we have prognostic factors that we know are important, such as age and MRI disease burden, there is still great uncertainty of the clinical course in the individual patient. If the topographical model can be further empirically validated using real world data, that could help us to predict what is going to happen to an individual patient. That can help us to make better treatment decisions for them because it could inform our treatment decisions in a more personalized way.

Is there any other recent research that supports these concepts?

DR. KRIEGER: We talk a lot about the need for biomarkers in MS to help us predict disease course and the topographical model makes the case that lesion location is a crucial biomarker. That is, the patient that has lesions in the spinal cord and the brain stem is more likely to have progressive signs and symptoms referable to those lesions.

A separate piece of work recently done by Keegan and colleagues that was published in Multiple Sclerosis Journal, looked at their own cohort of patients that had at least one critically located lesion, typically in the high cervical spinal cord or the lower brain stem, as being the crucial driver of the development of motor dysfunction and progressive disability.

In an editorial I wrote with my colleague, Fred Lublin, called “Location, location, location,” we point out that this is in some ways the best data in support of the concept of the topographical model that I have seen. It outlines a framework or a methodology where the importance of lesion location in defining the clinical picture and the risk of progression for an individual patient can be studied.

We interviewed Dr. Stephen Krieger to discuss his research in the implementation of the topographical model of Multiple Sclerosis.

What is the concept behind the topographical model of multiple sclerosis (MS)?

DR. KRIEGER: MS is an incredibly heterogeneous, and in many ways, unpredictable disease. Some people with MS will have a relapsing course, others will take a progressive course of disease, and many will have a disease course that spans both a relapsing phase and a progressive phase.

We have traditionally divided MS into phenotypes like relapsing-remitting MS (RRMS), secondary-progressive MS (SPMS), or primary-progressive MS (PPMS), and these phenotypes have been foundational in our field and used to define clinical trial cohorts and outcomes. They also have been used for the approval of our medicines. In practice, however, it sometimes can be difficult to know precisely what kind of MS, what phenotypes of MS, that an individual patient has.

The topographical model, which was proposed four years ago, tries to unify our concepts of MS in a way that spans across those phenotypes and animates the disease course in a more dynamic way to bridge from one phenotype to another.

As an individual patient, for example, develops clinically isolated syndrome (CIS) or first attack, and then RRMS, and then later SPMS, that gets depicted in a dynamic visualization through the topographical model. The model also makes use of the idea that where an MS lesion is in the central nervous system (CNS) defines the clinical symptoms that it causes.

This is something that we have long known, and the art of localization in neurology has existed for at least a couple hundred years. But we have not used that in the way we have depicted MS clinical course in recent decades. The topographical model tries to bring this idea of mapping an individual patient’s disease topography back into the clinical picture.

 In the topographical model, the lesions are shown as different topographical peaks, via the hills and valleys of areas of MS damage across different regions of the CNS [image]. They are compensated for by reserve, by the ability that the nervous system has to compensate and to keep a disease process from crossing the clinical threshold and causing symptoms.  What the topographical model displays is that  patients with MS lose reserve as time passes.

We know that there is brain atrophy, brain stem atrophy, spinal cord atrophy, and retinal nerve fiber layer thinning in this disease. The topographical model takes the concept that MS causes a loss of tissue across the CNS and applies it to where the lesions are in the CNS. The coming together of those two things brings about the clinical picture unmasking the deficit from those lesions over time. The short version is a depiction of disease course in MS. The way it looks has been likened to a leaking swimming pool, where there is a shallow end and a deep end, and as reserve drains over time more and more of that subclinical disease becomes unmasked.

In the Laitman article (2018), you applied the model to real patients. What were the main findings from that study?

DR. KRIEGER: Until now, the topographical model has been conceptual with a visual depiction, and I think it has been important as an educational tool and an aid to help shape our thinking about MS in a unified way.

The Laitman et al research, is the first time we have applied the concepts of the model to individual patients to confirm whether we could map individual patients’ MS histories in the topographical model and see if we could depict their clinical course this way. We found that we could.

One of the most important points that the topographical model makes is the idea that as progression occurs and reserve is lost, there is an unmasking of underlying disease. Meaning, all of the signs and symptoms that a patient has had during their relapse when they were accumulating lesions should be re-revealed or recapitulated when reserve is lost and progression occurs.

To confirm this, we mapped ten patients in the topographical model. We characterized their signs and symptoms of relapses during the relapsing phase and we found that the vast majority of these symptoms had redeclared themselves at the time that these patients developed SPMS. Furthermore,  those symptoms were continuing to worsen in their pattern; that is in the pattern of their disease topography as the years have continued to pass since they developed SPMS.

This was the first empirical study in real patients to show that the principles of the topographical model held true. This recapitulation hypothesis of symptoms in progressive disease was borne out, and that can help to lay the groundwork for future empirical studies to see how this model can be used as a predictive tool.

How does this new theory of MS disease progression better inform treatment decisions than the disease course theories that currently exist?

DR. KRIEGER: We have had the clinical phenotypes for 20 years and it has been very helpful to us in the development of treatments that we have shown are effective for RRMS and in more recent years for PPMS. What we don’t really have is a way of personalizing and predicting the individual person’s disease trajectory.

Although we have prognostic factors that we know are important, such as age and MRI disease burden, there is still great uncertainty of the clinical course in the individual patient. If the topographical model can be further empirically validated using real world data, that could help us to predict what is going to happen to an individual patient. That can help us to make better treatment decisions for them because it could inform our treatment decisions in a more personalized way.

Is there any other recent research that supports these concepts?

DR. KRIEGER: We talk a lot about the need for biomarkers in MS to help us predict disease course and the topographical model makes the case that lesion location is a crucial biomarker. That is, the patient that has lesions in the spinal cord and the brain stem is more likely to have progressive signs and symptoms referable to those lesions.

A separate piece of work recently done by Keegan and colleagues that was published in Multiple Sclerosis Journal, looked at their own cohort of patients that had at least one critically located lesion, typically in the high cervical spinal cord or the lower brain stem, as being the crucial driver of the development of motor dysfunction and progressive disability.

In an editorial I wrote with my colleague, Fred Lublin, called “Location, location, location,” we point out that this is in some ways the best data in support of the concept of the topographical model that I have seen. It outlines a framework or a methodology where the importance of lesion location in defining the clinical picture and the risk of progression for an individual patient can be studied.

In this edition of “How I will treat my next patient,” I take a look at two recent trials – one summarizes a presentation at the European Lung Cancer Congress on the value of durvalumab as adjuvant treatment in patients with locally-advanced non–small cell lung cancer and the other confirms the safety and efficacy of subcutaneously-administered trastuzumab as neoadjuvant treatment in HER2/-positive breast cancer patients.

PACIFIC trial

In the PACIFIC trial, 713 patients with unresectable, stage III non–small cell lung cancer (NSCLC) who received concurrent chemoradiation were randomized to receive adjuvant durvalumab or an identical placebo, for a year after radiation ended. The results were dramatic in favor of durvalumab (N Engl J Med. 2018;379:2342-50).

Durvalumab showed 24-month overall survival of 66.3% versus 55.6% with placebo (hazard ratio, 0.68, P = .0025) and progression-free survival of 17.2 months versus 5. 6 months (HR, 0.51). As expected, there were more grade 3-4 toxicities and treatment discontinuations with durvalumab than with placebo, but the toxicity seemed modest, given the substantial improvements in tumor-related outcomes.

At the recent European Lung Cancer Congress, Marina Garassino, MD, reported on Patient-Reported Outcomes (PRO) in PACIFIC. PROs were analyzed by PD-L1 level. A total of 63% of patients had PD-L1 tumor expression data for analysis. Overall, there were no major differences in PROs by PD-L1. Global quality of life did not differ by PD-L1 expression cohort.



These data support adjuvant durvalumab for stage III, chemoradiation-treated NSCLC patients, not only from efficacy and toxicity viewpoints, but also from the standpoint of the patient experience, independent of PD-L1 tumor expression.
 

What this means in practice

From every relevant perspective, regardless of histology and molecular features associated with their particular tumor, it is worthwhile for us to recommend – and for our patients to receive – durvalumab adjuvant therapy for up to 1 year after radiation ends, with close follow-up and adherence to the criteria for treatment modification or discontinuation as performed in the PACIFIC trial. These new data remove any lingering concerns about the value of this life-prolonging treatment.

Subcutaneous vs. IV trastuzumab

In this international phase 3 trial in early breast cancer patients, neoadjuvant chemotherapy was paired with either standard IV trastuzumab or subcutaneous trastuzumab at intervals of every 3 weeks. After the cytotoxic chemotherapy concluded, patients completed a 12-month course of trastuzumab with either the IV or subcutaneous administration, as previously randomized. The 6-year event-free survival and overall survival were 65% and 84%, respectively, for both the IV and subcutaneous treatment administration.

The authors concluded that these results are relevant to patients with low-risk HER2-positive breast cancer patients, for whom T-DM1 is not needed (JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339).

What this means in practice

These long-term data from the HannaH trial show persuasively that patients should be offered the more convenient, hopefully cheaper, subcutaneous route of administration. Since relapses beyond year 6 are unlikely, these data are unlikely to change with further follow-up. At our hospital, we recently made the decision to add subcutaneous trastuzumab to our formulary.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at two recent trials – one summarizes a presentation at the European Lung Cancer Congress on the value of durvalumab as adjuvant treatment in patients with locally-advanced non–small cell lung cancer and the other confirms the safety and efficacy of subcutaneously-administered trastuzumab as neoadjuvant treatment in HER2/-positive breast cancer patients.

PACIFIC trial

In the PACIFIC trial, 713 patients with unresectable, stage III non–small cell lung cancer (NSCLC) who received concurrent chemoradiation were randomized to receive adjuvant durvalumab or an identical placebo, for a year after radiation ended. The results were dramatic in favor of durvalumab (N Engl J Med. 2018;379:2342-50).

Durvalumab showed 24-month overall survival of 66.3% versus 55.6% with placebo (hazard ratio, 0.68, P = .0025) and progression-free survival of 17.2 months versus 5. 6 months (HR, 0.51). As expected, there were more grade 3-4 toxicities and treatment discontinuations with durvalumab than with placebo, but the toxicity seemed modest, given the substantial improvements in tumor-related outcomes.

At the recent European Lung Cancer Congress, Marina Garassino, MD, reported on Patient-Reported Outcomes (PRO) in PACIFIC. PROs were analyzed by PD-L1 level. A total of 63% of patients had PD-L1 tumor expression data for analysis. Overall, there were no major differences in PROs by PD-L1. Global quality of life did not differ by PD-L1 expression cohort.



These data support adjuvant durvalumab for stage III, chemoradiation-treated NSCLC patients, not only from efficacy and toxicity viewpoints, but also from the standpoint of the patient experience, independent of PD-L1 tumor expression.
 

What this means in practice

From every relevant perspective, regardless of histology and molecular features associated with their particular tumor, it is worthwhile for us to recommend – and for our patients to receive – durvalumab adjuvant therapy for up to 1 year after radiation ends, with close follow-up and adherence to the criteria for treatment modification or discontinuation as performed in the PACIFIC trial. These new data remove any lingering concerns about the value of this life-prolonging treatment.

Subcutaneous vs. IV trastuzumab

In this international phase 3 trial in early breast cancer patients, neoadjuvant chemotherapy was paired with either standard IV trastuzumab or subcutaneous trastuzumab at intervals of every 3 weeks. After the cytotoxic chemotherapy concluded, patients completed a 12-month course of trastuzumab with either the IV or subcutaneous administration, as previously randomized. The 6-year event-free survival and overall survival were 65% and 84%, respectively, for both the IV and subcutaneous treatment administration.

The authors concluded that these results are relevant to patients with low-risk HER2-positive breast cancer patients, for whom T-DM1 is not needed (JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339).

What this means in practice

These long-term data from the HannaH trial show persuasively that patients should be offered the more convenient, hopefully cheaper, subcutaneous route of administration. Since relapses beyond year 6 are unlikely, these data are unlikely to change with further follow-up. At our hospital, we recently made the decision to add subcutaneous trastuzumab to our formulary.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at two recent trials – one summarizes a presentation at the European Lung Cancer Congress on the value of durvalumab as adjuvant treatment in patients with locally-advanced non–small cell lung cancer and the other confirms the safety and efficacy of subcutaneously-administered trastuzumab as neoadjuvant treatment in HER2/-positive breast cancer patients.

PACIFIC trial

In the PACIFIC trial, 713 patients with unresectable, stage III non–small cell lung cancer (NSCLC) who received concurrent chemoradiation were randomized to receive adjuvant durvalumab or an identical placebo, for a year after radiation ended. The results were dramatic in favor of durvalumab (N Engl J Med. 2018;379:2342-50).

Durvalumab showed 24-month overall survival of 66.3% versus 55.6% with placebo (hazard ratio, 0.68, P = .0025) and progression-free survival of 17.2 months versus 5. 6 months (HR, 0.51). As expected, there were more grade 3-4 toxicities and treatment discontinuations with durvalumab than with placebo, but the toxicity seemed modest, given the substantial improvements in tumor-related outcomes.

At the recent European Lung Cancer Congress, Marina Garassino, MD, reported on Patient-Reported Outcomes (PRO) in PACIFIC. PROs were analyzed by PD-L1 level. A total of 63% of patients had PD-L1 tumor expression data for analysis. Overall, there were no major differences in PROs by PD-L1. Global quality of life did not differ by PD-L1 expression cohort.



These data support adjuvant durvalumab for stage III, chemoradiation-treated NSCLC patients, not only from efficacy and toxicity viewpoints, but also from the standpoint of the patient experience, independent of PD-L1 tumor expression.
 

What this means in practice

From every relevant perspective, regardless of histology and molecular features associated with their particular tumor, it is worthwhile for us to recommend – and for our patients to receive – durvalumab adjuvant therapy for up to 1 year after radiation ends, with close follow-up and adherence to the criteria for treatment modification or discontinuation as performed in the PACIFIC trial. These new data remove any lingering concerns about the value of this life-prolonging treatment.

Subcutaneous vs. IV trastuzumab

In this international phase 3 trial in early breast cancer patients, neoadjuvant chemotherapy was paired with either standard IV trastuzumab or subcutaneous trastuzumab at intervals of every 3 weeks. After the cytotoxic chemotherapy concluded, patients completed a 12-month course of trastuzumab with either the IV or subcutaneous administration, as previously randomized. The 6-year event-free survival and overall survival were 65% and 84%, respectively, for both the IV and subcutaneous treatment administration.

The authors concluded that these results are relevant to patients with low-risk HER2-positive breast cancer patients, for whom T-DM1 is not needed (JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339).

What this means in practice

These long-term data from the HannaH trial show persuasively that patients should be offered the more convenient, hopefully cheaper, subcutaneous route of administration. Since relapses beyond year 6 are unlikely, these data are unlikely to change with further follow-up. At our hospital, we recently made the decision to add subcutaneous trastuzumab to our formulary.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.