AVAHO

Atezolizumab (Tecentriq) is no longer approved in the United States for use in certain patients with bladder or urinary tract cancer.

The drug is an anti–PD-L1 inhibitor immunotherapy, and continues to be approved for use in lung and liver cancer and melanoma.

The manufacturer, Genentech, announced that it was voluntarily withdrawing the U.S. indication for atezolizumab that covered its use in adults with locally advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

The company said that it made the decision after consultation with the Food and Drug Administration.

“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development.

Atezolizumab had been granted an accelerated approval for this indication back in 2016, based on response rate data from the IMvigor210 trial.

The company was obliged to conduct a follow-up trial to show clinical benefit, and launched IMvigor130, which it described as “the designated postmarketing requirement to convert the accelerated approval to regular approval.”

The bladder cancer indication for atezolizumab was discussed (alongside several other indications for different immunotherapy drugs) at a historic 3-day meeting of the FDA’s oncologic Drugs Advisory Committee in April 2021. At the time, ODAC voted 10-1 in favor of maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

Genentech has now said that this trial “did not meet the coprimary endpoint of overall survival for atezolizumab plus chemotherapy compared with chemotherapy alone” when used for the first-line treatment of patients with previously untreated advanced bladder cancer.

These data will be presented at an upcoming medical meeting, the company added.

“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Dr. Garraway commented.

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

Atezolizumab (Tecentriq) is no longer approved in the United States for use in certain patients with bladder or urinary tract cancer.

The drug is an anti–PD-L1 inhibitor immunotherapy, and continues to be approved for use in lung and liver cancer and melanoma.

The manufacturer, Genentech, announced that it was voluntarily withdrawing the U.S. indication for atezolizumab that covered its use in adults with locally advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

The company said that it made the decision after consultation with the Food and Drug Administration.

“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development.

Atezolizumab had been granted an accelerated approval for this indication back in 2016, based on response rate data from the IMvigor210 trial.

The company was obliged to conduct a follow-up trial to show clinical benefit, and launched IMvigor130, which it described as “the designated postmarketing requirement to convert the accelerated approval to regular approval.”

The bladder cancer indication for atezolizumab was discussed (alongside several other indications for different immunotherapy drugs) at a historic 3-day meeting of the FDA’s oncologic Drugs Advisory Committee in April 2021. At the time, ODAC voted 10-1 in favor of maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

Genentech has now said that this trial “did not meet the coprimary endpoint of overall survival for atezolizumab plus chemotherapy compared with chemotherapy alone” when used for the first-line treatment of patients with previously untreated advanced bladder cancer.

These data will be presented at an upcoming medical meeting, the company added.

“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Dr. Garraway commented.

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

Atezolizumab (Tecentriq) is no longer approved in the United States for use in certain patients with bladder or urinary tract cancer.

The drug is an anti–PD-L1 inhibitor immunotherapy, and continues to be approved for use in lung and liver cancer and melanoma.

The manufacturer, Genentech, announced that it was voluntarily withdrawing the U.S. indication for atezolizumab that covered its use in adults with locally advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

The company said that it made the decision after consultation with the Food and Drug Administration.

“While we are disappointed with this withdrawal, we understand the need to uphold the principles of the FDA’s Accelerated Approval Program, which brings innovative medicines to patients sooner,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of Global Product Development.

Atezolizumab had been granted an accelerated approval for this indication back in 2016, based on response rate data from the IMvigor210 trial.

The company was obliged to conduct a follow-up trial to show clinical benefit, and launched IMvigor130, which it described as “the designated postmarketing requirement to convert the accelerated approval to regular approval.”

The bladder cancer indication for atezolizumab was discussed (alongside several other indications for different immunotherapy drugs) at a historic 3-day meeting of the FDA’s oncologic Drugs Advisory Committee in April 2021. At the time, ODAC voted 10-1 in favor of maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

Genentech has now said that this trial “did not meet the coprimary endpoint of overall survival for atezolizumab plus chemotherapy compared with chemotherapy alone” when used for the first-line treatment of patients with previously untreated advanced bladder cancer.

These data will be presented at an upcoming medical meeting, the company added.

“There is a considerable unmet need for effective and tolerable treatments for people living with advanced bladder cancer and so we regret that the IMvigor130 trial did not cross the statistical threshold for overall survival,” Dr. Garraway commented.

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

Among high-risk early breast cancer patients, a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from a phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.

“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.

“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.

The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.

Among high-risk early breast cancer patients, a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from a phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.

“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.

“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.

The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.

Among high-risk early breast cancer patients, a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from a phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from 6 weeks down to 3 weeks. And, they showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant at a press conference held at the annual meeting of the American Society for Radiation Oncology where the findings were presented.

“This is substantially more convenient. It is cost effective, both for the health care system and for individual patients. Importantly, our patients come in for treatment every day. They’re taking time off of work, they have to arrange for childcare, and they have to arrange for transportation. So this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

The study was presented by Frank A. Vicini, MD, FASTRO, a radiation oncologist with GenesisCare, Farmington Hills, Mich.

“One of the things I think that was surprising is I think all of us were thinking that this might be a more toxic regimen, but as Dr. Vincini showed, over time it was equally effective and with minimal toxicity, and cosmesis over time was stable, and that’s important. Importantly, that included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It is an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized, controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation is in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice is for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds a week to a week and a half to treatment length.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar, with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score to assess outcomes from the perspective of both physicians and patients; 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation as compared to a sequential boost, results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient-rated cosmesis, no significant difference in physician rated cosmesis, and delivering the entire treatment even at high risk patients in 3 weeks. Just as critical, the use of target volume–based radiation planning for 3-D [three-dimensional] conformal or [intensity-modulated radiation therapy] whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” said Dr. Vincini during the press conference.

The study was grant funded. Neither Dr. Vincini nor Dr. Horst had relevant financial disclosures.

DENVER – As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

DENVER – As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

DENVER – As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

Latinx individuals have a lower overall risk of melanoma than non-Latinx Whites (NLW), but they are more likely to be diagnosed with advanced disease, and experience greater mortality. A new qualitative study of Latinx and low-income NLW individuals in California has revealed some of the socioeconomic and community factors that may play a role in preventing early access to care.

Thicker melanomas, which are more likely to be lethal, are on the rise in the United States among people with lower socioeconomic status (SES), as well as African Americans and Hispanics, and both Black and Latinx people are more likely than NLW people to present with stage 3 or stage 4 disease. “That has really prompted us to look at community engagement and outreach and then really understand the qualitative aspects that are driving individuals into higher risk for melanoma, apart from just limited insurance and access to health care,” said Susan Swetter, MD, who presented the results of the study at the annual meeting of the American Society of Clinical Oncology.

Other studies, such as a Boston-area survey published in 2020, suggest that Hispanics are less likely than Whites to know the meaning of the term melanoma (odds ratio, 0.27; P =.0037), suggesting the need for educational efforts. The authors of that study noted that knowledge of melanoma in 2017, when the survey was conducted, remained essentially unchanged since a previous study was published in 1996.

“Our results support a need for better public educational programs, particularly those geared toward minority populations. Educational programs that are culturally relevant and include specific sections for skin of color have been shown to better promote early melanoma detection in individuals of ethnic minorities and may help decrease the ethnic disparities in melanoma-related mortality. At the patient-physician level, dermatologists may educate their patients, including Hispanic patients, should they choose to perform (skin self-examinations) to specifically inspect the extremities and acral areas, given the higher incidence rates of melanoma on those areas in this population,” the authors wrote.

The goal of the new study is to get a better understanding of the factors that affect attitudes toward health care, and the researchers found a complex mixture that including ethnicity, cultural, gender identity, geography, skin color, gender norms, and socioeconomic status (SES). “Qualitative research can inform our preventive and early detection strategies. For instance, in the Latinx group, there’s a lot of mistrust of health systems, medical providers, and who is providing that knowledge. We have to figure out ways to provide a trusted source of information. Doctors and physicians and health providers tend to be trusted, but there are many barriers to getting lower SES patients into care. We’re now investigating the use of community health workers and even individuals in various settings and community centers, religious settings or religious leaders, where we’ve determined through this focus group research that there is increased trust,” Dr. Swetter said.

The researchers assembled 19 focus groups with 176 total adult participants, interviewing them about perceptions of melanoma risk, prevention and screening strategies and their acceptability, and barriers to melanoma prevention and care. The sample include people from urban and semirural areas; 55%-62% of participants self-identified as Latinx or Hispanic and 26%-27% as NLW.

Latinx and semirural participants reported having minimal conversations with family about melanoma prevention, and those who reported having darker skin perceived their risk from skin cancer as lower. Participants who lived in rural areas, were Latinx, or of low SES status indicated that health care access challenges included out-of-pocket costs, past experiences of physicians showing less concern about them, and little confidence that rural physicians had the needed expertise or would make an appropriate referral.

The study is just the first step in a series of efforts to improve melanoma outcomes in high-risk populations, which is being pursued through Stanford University’s Wipe Out Melanoma–California statewide initiative and research consortium. “What we aim to do is use this knowledge to now design programs to reach the populations who are more likely to present with worse disease, and to prevent that disease from happening. These qualitative analyses are few and far between in the world of melanoma, and we’re really happy to really push this envelope and change the way we deliver preventive and early detection efforts,” said Dr. Swetter, who is a professor of dermatology and director of the pigmented lesion/melanoma and cutaneous oncology programs at Stanford (Calif.) University Medical Center. Dr. Swetter also chairs the National Comprehensive Cancer Network guidelines for cutaneous melanoma.

The study could also improve care of advanced melanoma. “There’s clear evidence that many of these patient and SES factors, economic and knowledge barriers are the same when it comes to getting patients with advanced melanoma into appropriate care and on clinical trials, and that’s true across all races and ethnicities,” said Dr. Swetter.

The ultimate goal of these approaches is to give individuals greater “self-efficacy, such that a person feels more competent to manage his or her own health outcomes. One aspect of this approach is the use of novel technology such as smartphone apps that can track moles or help visualize lesions during teledermatology. “I think that the future of melanoma prevention and early detection is bright, especially if we incorporate novel technologies and engage patients and their communities in the effort. It’s a different strategy, as opposed to the top-down approach of physicians imparting knowledge and providing the exam. Increasing community engagement is critical to reaching the populations at highest risk for advanced disease and getting them into care and detection early,” Dr. Swetter said.

Dr. Swetter has no relevant financial disclosures.

Latinx individuals have a lower overall risk of melanoma than non-Latinx Whites (NLW), but they are more likely to be diagnosed with advanced disease, and experience greater mortality. A new qualitative study of Latinx and low-income NLW individuals in California has revealed some of the socioeconomic and community factors that may play a role in preventing early access to care.

Thicker melanomas, which are more likely to be lethal, are on the rise in the United States among people with lower socioeconomic status (SES), as well as African Americans and Hispanics, and both Black and Latinx people are more likely than NLW people to present with stage 3 or stage 4 disease. “That has really prompted us to look at community engagement and outreach and then really understand the qualitative aspects that are driving individuals into higher risk for melanoma, apart from just limited insurance and access to health care,” said Susan Swetter, MD, who presented the results of the study at the annual meeting of the American Society of Clinical Oncology.

Other studies, such as a Boston-area survey published in 2020, suggest that Hispanics are less likely than Whites to know the meaning of the term melanoma (odds ratio, 0.27; P =.0037), suggesting the need for educational efforts. The authors of that study noted that knowledge of melanoma in 2017, when the survey was conducted, remained essentially unchanged since a previous study was published in 1996.

“Our results support a need for better public educational programs, particularly those geared toward minority populations. Educational programs that are culturally relevant and include specific sections for skin of color have been shown to better promote early melanoma detection in individuals of ethnic minorities and may help decrease the ethnic disparities in melanoma-related mortality. At the patient-physician level, dermatologists may educate their patients, including Hispanic patients, should they choose to perform (skin self-examinations) to specifically inspect the extremities and acral areas, given the higher incidence rates of melanoma on those areas in this population,” the authors wrote.

The goal of the new study is to get a better understanding of the factors that affect attitudes toward health care, and the researchers found a complex mixture that including ethnicity, cultural, gender identity, geography, skin color, gender norms, and socioeconomic status (SES). “Qualitative research can inform our preventive and early detection strategies. For instance, in the Latinx group, there’s a lot of mistrust of health systems, medical providers, and who is providing that knowledge. We have to figure out ways to provide a trusted source of information. Doctors and physicians and health providers tend to be trusted, but there are many barriers to getting lower SES patients into care. We’re now investigating the use of community health workers and even individuals in various settings and community centers, religious settings or religious leaders, where we’ve determined through this focus group research that there is increased trust,” Dr. Swetter said.

The researchers assembled 19 focus groups with 176 total adult participants, interviewing them about perceptions of melanoma risk, prevention and screening strategies and their acceptability, and barriers to melanoma prevention and care. The sample include people from urban and semirural areas; 55%-62% of participants self-identified as Latinx or Hispanic and 26%-27% as NLW.

Latinx and semirural participants reported having minimal conversations with family about melanoma prevention, and those who reported having darker skin perceived their risk from skin cancer as lower. Participants who lived in rural areas, were Latinx, or of low SES status indicated that health care access challenges included out-of-pocket costs, past experiences of physicians showing less concern about them, and little confidence that rural physicians had the needed expertise or would make an appropriate referral.

The study is just the first step in a series of efforts to improve melanoma outcomes in high-risk populations, which is being pursued through Stanford University’s Wipe Out Melanoma–California statewide initiative and research consortium. “What we aim to do is use this knowledge to now design programs to reach the populations who are more likely to present with worse disease, and to prevent that disease from happening. These qualitative analyses are few and far between in the world of melanoma, and we’re really happy to really push this envelope and change the way we deliver preventive and early detection efforts,” said Dr. Swetter, who is a professor of dermatology and director of the pigmented lesion/melanoma and cutaneous oncology programs at Stanford (Calif.) University Medical Center. Dr. Swetter also chairs the National Comprehensive Cancer Network guidelines for cutaneous melanoma.

The study could also improve care of advanced melanoma. “There’s clear evidence that many of these patient and SES factors, economic and knowledge barriers are the same when it comes to getting patients with advanced melanoma into appropriate care and on clinical trials, and that’s true across all races and ethnicities,” said Dr. Swetter.

The ultimate goal of these approaches is to give individuals greater “self-efficacy, such that a person feels more competent to manage his or her own health outcomes. One aspect of this approach is the use of novel technology such as smartphone apps that can track moles or help visualize lesions during teledermatology. “I think that the future of melanoma prevention and early detection is bright, especially if we incorporate novel technologies and engage patients and their communities in the effort. It’s a different strategy, as opposed to the top-down approach of physicians imparting knowledge and providing the exam. Increasing community engagement is critical to reaching the populations at highest risk for advanced disease and getting them into care and detection early,” Dr. Swetter said.

Dr. Swetter has no relevant financial disclosures.

Latinx individuals have a lower overall risk of melanoma than non-Latinx Whites (NLW), but they are more likely to be diagnosed with advanced disease, and experience greater mortality. A new qualitative study of Latinx and low-income NLW individuals in California has revealed some of the socioeconomic and community factors that may play a role in preventing early access to care.

Thicker melanomas, which are more likely to be lethal, are on the rise in the United States among people with lower socioeconomic status (SES), as well as African Americans and Hispanics, and both Black and Latinx people are more likely than NLW people to present with stage 3 or stage 4 disease. “That has really prompted us to look at community engagement and outreach and then really understand the qualitative aspects that are driving individuals into higher risk for melanoma, apart from just limited insurance and access to health care,” said Susan Swetter, MD, who presented the results of the study at the annual meeting of the American Society of Clinical Oncology.

Other studies, such as a Boston-area survey published in 2020, suggest that Hispanics are less likely than Whites to know the meaning of the term melanoma (odds ratio, 0.27; P =.0037), suggesting the need for educational efforts. The authors of that study noted that knowledge of melanoma in 2017, when the survey was conducted, remained essentially unchanged since a previous study was published in 1996.

“Our results support a need for better public educational programs, particularly those geared toward minority populations. Educational programs that are culturally relevant and include specific sections for skin of color have been shown to better promote early melanoma detection in individuals of ethnic minorities and may help decrease the ethnic disparities in melanoma-related mortality. At the patient-physician level, dermatologists may educate their patients, including Hispanic patients, should they choose to perform (skin self-examinations) to specifically inspect the extremities and acral areas, given the higher incidence rates of melanoma on those areas in this population,” the authors wrote.

The goal of the new study is to get a better understanding of the factors that affect attitudes toward health care, and the researchers found a complex mixture that including ethnicity, cultural, gender identity, geography, skin color, gender norms, and socioeconomic status (SES). “Qualitative research can inform our preventive and early detection strategies. For instance, in the Latinx group, there’s a lot of mistrust of health systems, medical providers, and who is providing that knowledge. We have to figure out ways to provide a trusted source of information. Doctors and physicians and health providers tend to be trusted, but there are many barriers to getting lower SES patients into care. We’re now investigating the use of community health workers and even individuals in various settings and community centers, religious settings or religious leaders, where we’ve determined through this focus group research that there is increased trust,” Dr. Swetter said.

The researchers assembled 19 focus groups with 176 total adult participants, interviewing them about perceptions of melanoma risk, prevention and screening strategies and their acceptability, and barriers to melanoma prevention and care. The sample include people from urban and semirural areas; 55%-62% of participants self-identified as Latinx or Hispanic and 26%-27% as NLW.

Latinx and semirural participants reported having minimal conversations with family about melanoma prevention, and those who reported having darker skin perceived their risk from skin cancer as lower. Participants who lived in rural areas, were Latinx, or of low SES status indicated that health care access challenges included out-of-pocket costs, past experiences of physicians showing less concern about them, and little confidence that rural physicians had the needed expertise or would make an appropriate referral.

The study is just the first step in a series of efforts to improve melanoma outcomes in high-risk populations, which is being pursued through Stanford University’s Wipe Out Melanoma–California statewide initiative and research consortium. “What we aim to do is use this knowledge to now design programs to reach the populations who are more likely to present with worse disease, and to prevent that disease from happening. These qualitative analyses are few and far between in the world of melanoma, and we’re really happy to really push this envelope and change the way we deliver preventive and early detection efforts,” said Dr. Swetter, who is a professor of dermatology and director of the pigmented lesion/melanoma and cutaneous oncology programs at Stanford (Calif.) University Medical Center. Dr. Swetter also chairs the National Comprehensive Cancer Network guidelines for cutaneous melanoma.

The study could also improve care of advanced melanoma. “There’s clear evidence that many of these patient and SES factors, economic and knowledge barriers are the same when it comes to getting patients with advanced melanoma into appropriate care and on clinical trials, and that’s true across all races and ethnicities,” said Dr. Swetter.

The ultimate goal of these approaches is to give individuals greater “self-efficacy, such that a person feels more competent to manage his or her own health outcomes. One aspect of this approach is the use of novel technology such as smartphone apps that can track moles or help visualize lesions during teledermatology. “I think that the future of melanoma prevention and early detection is bright, especially if we incorporate novel technologies and engage patients and their communities in the effort. It’s a different strategy, as opposed to the top-down approach of physicians imparting knowledge and providing the exam. Increasing community engagement is critical to reaching the populations at highest risk for advanced disease and getting them into care and detection early,” Dr. Swetter said.

Dr. Swetter has no relevant financial disclosures.

The combination of nivolumab and vidutolimod led to a high rate of pathologic complete response and pathologic major response in a phase 2 trial of patients with stage 3 resectable melanoma. The result led researchers to call for a future study comparing the regimen against a suitable control group.

“We were very excited to see the ability of intratumoral vidutolimod to augment T-cell infiltrate. (Pathologic) response was associated with a dense infiltrate of CD8 T cells. We were also able to demonstrate for what I think may be the first time, that intratumoral CpG resulted in clear evidence of CD303+ plasmacytoid dendritic cells [pDCs],” said Diwakar Davar, MD, assistant professor of medicine at the University of Pittsburgh, during a presentation of the results at the annual meeting of the Society for Immunotherapy of Cancer. He noted that pDCs represent a very rare cell population, less than 0.4% of circulating peripheral blood mononuclear cells, and tend to be found in lymph nodes.

The current standard of care for stage 3 melanoma is up-front surgery followed by adjuvant therapy – anti–PD-1 therapy for patients with wild-type or BRAF-mutant cancers, and targeted therapy with BRAF/MEK inhibitors in patients with BRAF mutations. However, preclinical studies suggest that neoadjuvant immunotherapy could lead to a stronger antitumor T-cell response than adjuvant immunotherapy.

Vidutolimod targets the toll-like receptor 9 (TLR-9) endosomal receptor found in B cells and pDC cells. The formulation is a virus-like particle (VLP) that contains unmethylated cytosine guanine–rich oligonucleotides (CpG ODN). Bacterial and viral genomes tend to be enriched in CpG ODN, and this acts as a TLR-9 agonist. TLR-9 activation in turn triggers an interferon response, and this may help overcome PD-1 blockade resistance in metastatic melanoma.

The researchers conducted a nonrandomized, open-label trial that included 30 patients with stage 3 melanoma (14 women; median age, 61 years). Patients received neoadjuvant nivolumab and vidutolimod for 8 weeks, then were evaluated for surgery. Patients continued both drugs in the adjuvant setting for 48 weeks. 47% experienced complete pathologic response, 10% a major pathologic response, and 10% a partial pathologic response.

Analysis of resected samples revealed clear evidence of an immune response, Dr. Davar said during a press conference held in advance of the meeting. “Pathologic response was associated with compelling evidence of immune activation both peripherally and within the tumor, with clear evidence of pDC infiltrate and pDC activation – something that has not previously been seen in human specimens.”

The study regimen appeared safe, with no dose-limiting toxicities or grade 4 or 5 adverse events. He noted that the regimen is now being tested in the phase 2 ECOG-ACRIN trial.

The results are “very exciting,” said Pamela Ohashi, PhD, who commented on the study during the press conference. The virus-like nature of vidutolimod may be an important element of the therapy. “I think scientifically we would have predicted that the VLP carrying the CPG would be very good at activating the CD8 cells, which in fact is what you’re seeing. So I think it’s very exciting and has lots of potential for future combinations,” said Dr. Ohashi, who is director of the tumor immunotherapy program at the Princess Margaret Cancer Centre, Toronto.

The study was funded by Checkmate Pharmaceuticals. Dr. Davar has financial relationships with Checkmate Pharmaceuticals and Regeneron, which has acquired Checkmate Pharmaceuticals.

The combination of nivolumab and vidutolimod led to a high rate of pathologic complete response and pathologic major response in a phase 2 trial of patients with stage 3 resectable melanoma. The result led researchers to call for a future study comparing the regimen against a suitable control group.

“We were very excited to see the ability of intratumoral vidutolimod to augment T-cell infiltrate. (Pathologic) response was associated with a dense infiltrate of CD8 T cells. We were also able to demonstrate for what I think may be the first time, that intratumoral CpG resulted in clear evidence of CD303+ plasmacytoid dendritic cells [pDCs],” said Diwakar Davar, MD, assistant professor of medicine at the University of Pittsburgh, during a presentation of the results at the annual meeting of the Society for Immunotherapy of Cancer. He noted that pDCs represent a very rare cell population, less than 0.4% of circulating peripheral blood mononuclear cells, and tend to be found in lymph nodes.

The current standard of care for stage 3 melanoma is up-front surgery followed by adjuvant therapy – anti–PD-1 therapy for patients with wild-type or BRAF-mutant cancers, and targeted therapy with BRAF/MEK inhibitors in patients with BRAF mutations. However, preclinical studies suggest that neoadjuvant immunotherapy could lead to a stronger antitumor T-cell response than adjuvant immunotherapy.

Vidutolimod targets the toll-like receptor 9 (TLR-9) endosomal receptor found in B cells and pDC cells. The formulation is a virus-like particle (VLP) that contains unmethylated cytosine guanine–rich oligonucleotides (CpG ODN). Bacterial and viral genomes tend to be enriched in CpG ODN, and this acts as a TLR-9 agonist. TLR-9 activation in turn triggers an interferon response, and this may help overcome PD-1 blockade resistance in metastatic melanoma.

The researchers conducted a nonrandomized, open-label trial that included 30 patients with stage 3 melanoma (14 women; median age, 61 years). Patients received neoadjuvant nivolumab and vidutolimod for 8 weeks, then were evaluated for surgery. Patients continued both drugs in the adjuvant setting for 48 weeks. 47% experienced complete pathologic response, 10% a major pathologic response, and 10% a partial pathologic response.

Analysis of resected samples revealed clear evidence of an immune response, Dr. Davar said during a press conference held in advance of the meeting. “Pathologic response was associated with compelling evidence of immune activation both peripherally and within the tumor, with clear evidence of pDC infiltrate and pDC activation – something that has not previously been seen in human specimens.”

The study regimen appeared safe, with no dose-limiting toxicities or grade 4 or 5 adverse events. He noted that the regimen is now being tested in the phase 2 ECOG-ACRIN trial.

The results are “very exciting,” said Pamela Ohashi, PhD, who commented on the study during the press conference. The virus-like nature of vidutolimod may be an important element of the therapy. “I think scientifically we would have predicted that the VLP carrying the CPG would be very good at activating the CD8 cells, which in fact is what you’re seeing. So I think it’s very exciting and has lots of potential for future combinations,” said Dr. Ohashi, who is director of the tumor immunotherapy program at the Princess Margaret Cancer Centre, Toronto.

The study was funded by Checkmate Pharmaceuticals. Dr. Davar has financial relationships with Checkmate Pharmaceuticals and Regeneron, which has acquired Checkmate Pharmaceuticals.

The combination of nivolumab and vidutolimod led to a high rate of pathologic complete response and pathologic major response in a phase 2 trial of patients with stage 3 resectable melanoma. The result led researchers to call for a future study comparing the regimen against a suitable control group.

“We were very excited to see the ability of intratumoral vidutolimod to augment T-cell infiltrate. (Pathologic) response was associated with a dense infiltrate of CD8 T cells. We were also able to demonstrate for what I think may be the first time, that intratumoral CpG resulted in clear evidence of CD303+ plasmacytoid dendritic cells [pDCs],” said Diwakar Davar, MD, assistant professor of medicine at the University of Pittsburgh, during a presentation of the results at the annual meeting of the Society for Immunotherapy of Cancer. He noted that pDCs represent a very rare cell population, less than 0.4% of circulating peripheral blood mononuclear cells, and tend to be found in lymph nodes.

The current standard of care for stage 3 melanoma is up-front surgery followed by adjuvant therapy – anti–PD-1 therapy for patients with wild-type or BRAF-mutant cancers, and targeted therapy with BRAF/MEK inhibitors in patients with BRAF mutations. However, preclinical studies suggest that neoadjuvant immunotherapy could lead to a stronger antitumor T-cell response than adjuvant immunotherapy.

Vidutolimod targets the toll-like receptor 9 (TLR-9) endosomal receptor found in B cells and pDC cells. The formulation is a virus-like particle (VLP) that contains unmethylated cytosine guanine–rich oligonucleotides (CpG ODN). Bacterial and viral genomes tend to be enriched in CpG ODN, and this acts as a TLR-9 agonist. TLR-9 activation in turn triggers an interferon response, and this may help overcome PD-1 blockade resistance in metastatic melanoma.

The researchers conducted a nonrandomized, open-label trial that included 30 patients with stage 3 melanoma (14 women; median age, 61 years). Patients received neoadjuvant nivolumab and vidutolimod for 8 weeks, then were evaluated for surgery. Patients continued both drugs in the adjuvant setting for 48 weeks. 47% experienced complete pathologic response, 10% a major pathologic response, and 10% a partial pathologic response.

Analysis of resected samples revealed clear evidence of an immune response, Dr. Davar said during a press conference held in advance of the meeting. “Pathologic response was associated with compelling evidence of immune activation both peripherally and within the tumor, with clear evidence of pDC infiltrate and pDC activation – something that has not previously been seen in human specimens.”

The study regimen appeared safe, with no dose-limiting toxicities or grade 4 or 5 adverse events. He noted that the regimen is now being tested in the phase 2 ECOG-ACRIN trial.

The results are “very exciting,” said Pamela Ohashi, PhD, who commented on the study during the press conference. The virus-like nature of vidutolimod may be an important element of the therapy. “I think scientifically we would have predicted that the VLP carrying the CPG would be very good at activating the CD8 cells, which in fact is what you’re seeing. So I think it’s very exciting and has lots of potential for future combinations,” said Dr. Ohashi, who is director of the tumor immunotherapy program at the Princess Margaret Cancer Centre, Toronto.

The study was funded by Checkmate Pharmaceuticals. Dr. Davar has financial relationships with Checkmate Pharmaceuticals and Regeneron, which has acquired Checkmate Pharmaceuticals.

The U.S. Food and Drug Administration has approved etranacogene dezaparvovec (Hemgenix), the first gene therapy option for adults with hemophilia B who currently use factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.*

“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”

Hemophilia B is caused by a deficiency in clotting factor IX attributable to a faulty gene. The newly approved IV infusion delivers a functional gene to liver cells via an adeno-associated virus that instructs them to make the clotting factor. The genetic instructions remain in the cell but aren’t incorporated into the patient’s own DNA, according to a press release from maker CSL Behring.

The gene therapy will cost $3.5 million, making it the most expensive treatment to date -- more than Bluebird's recently approved gene therapies. A recent analysis from the Institute for Clinical and Economic Review said charging $2.93-$2.96 million would be justified because etranacogene dezaparvovec would offset the need for ongoing factor IX replacement, which can top $20 million over a lifetime.

Approval was based on the single-arm, open-label HOPE-B trial in 54 men who relied on factor IX replacement therapy; most patients with hemophilia B are male.

Over the 18 months after infusion, their adjusted annualized bleeding rate fell 64% compared with baseline (P = .0002), and factor IX–treated bleeds fell 77% (P < .0001); 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued factor IX prophylaxis.

Durability of the effect remains a concern, but data have been reassuring, with subjects having a mean factor IX activity of 39 IU/dL at 6 months – 39% of normal – and 36.9 IU/dL at 18 months, about 37% of normal. There’s been no sign so far of patients developing inhibitors against the infusion.

Adverse events were common but largely mild and included headache and influenza-like illness, both in 13% of subjects. Nine patients needed steroids for liver enzyme elevations.

The trial was temporarily halted due to a case of liver cancer, but it was ultimately deemed not to be related to treatment, based on molecular tumor characterization and vector integration analysis. A death in the trial was also not considered treatment related.

Other gene therapies are in the pipeline for hemophilia, including valoctocogene roxaparvovec (Roctavian, BioMarin) for hemophilia A. FDA’s approval decision is expected in March 2023.

This article was updated 11/23/22.

Correction, 11/23/22: The brand name Hemgenix was misstated in an earlier version of this article.

The U.S. Food and Drug Administration has approved etranacogene dezaparvovec (Hemgenix), the first gene therapy option for adults with hemophilia B who currently use factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.*

“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”

Hemophilia B is caused by a deficiency in clotting factor IX attributable to a faulty gene. The newly approved IV infusion delivers a functional gene to liver cells via an adeno-associated virus that instructs them to make the clotting factor. The genetic instructions remain in the cell but aren’t incorporated into the patient’s own DNA, according to a press release from maker CSL Behring.

The gene therapy will cost $3.5 million, making it the most expensive treatment to date -- more than Bluebird's recently approved gene therapies. A recent analysis from the Institute for Clinical and Economic Review said charging $2.93-$2.96 million would be justified because etranacogene dezaparvovec would offset the need for ongoing factor IX replacement, which can top $20 million over a lifetime.

Approval was based on the single-arm, open-label HOPE-B trial in 54 men who relied on factor IX replacement therapy; most patients with hemophilia B are male.

Over the 18 months after infusion, their adjusted annualized bleeding rate fell 64% compared with baseline (P = .0002), and factor IX–treated bleeds fell 77% (P < .0001); 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued factor IX prophylaxis.

Durability of the effect remains a concern, but data have been reassuring, with subjects having a mean factor IX activity of 39 IU/dL at 6 months – 39% of normal – and 36.9 IU/dL at 18 months, about 37% of normal. There’s been no sign so far of patients developing inhibitors against the infusion.

Adverse events were common but largely mild and included headache and influenza-like illness, both in 13% of subjects. Nine patients needed steroids for liver enzyme elevations.

The trial was temporarily halted due to a case of liver cancer, but it was ultimately deemed not to be related to treatment, based on molecular tumor characterization and vector integration analysis. A death in the trial was also not considered treatment related.

Other gene therapies are in the pipeline for hemophilia, including valoctocogene roxaparvovec (Roctavian, BioMarin) for hemophilia A. FDA’s approval decision is expected in March 2023.

This article was updated 11/23/22.

Correction, 11/23/22: The brand name Hemgenix was misstated in an earlier version of this article.

The U.S. Food and Drug Administration has approved etranacogene dezaparvovec (Hemgenix), the first gene therapy option for adults with hemophilia B who currently use factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes.*

“Gene therapy for hemophilia has been on the horizon for more than 2 decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”

Hemophilia B is caused by a deficiency in clotting factor IX attributable to a faulty gene. The newly approved IV infusion delivers a functional gene to liver cells via an adeno-associated virus that instructs them to make the clotting factor. The genetic instructions remain in the cell but aren’t incorporated into the patient’s own DNA, according to a press release from maker CSL Behring.

The gene therapy will cost $3.5 million, making it the most expensive treatment to date -- more than Bluebird's recently approved gene therapies. A recent analysis from the Institute for Clinical and Economic Review said charging $2.93-$2.96 million would be justified because etranacogene dezaparvovec would offset the need for ongoing factor IX replacement, which can top $20 million over a lifetime.

Approval was based on the single-arm, open-label HOPE-B trial in 54 men who relied on factor IX replacement therapy; most patients with hemophilia B are male.

Over the 18 months after infusion, their adjusted annualized bleeding rate fell 64% compared with baseline (P = .0002), and factor IX–treated bleeds fell 77% (P < .0001); 98% of subjects treated with a full dose of etranacogene dezaparvovec discontinued factor IX prophylaxis.

Durability of the effect remains a concern, but data have been reassuring, with subjects having a mean factor IX activity of 39 IU/dL at 6 months – 39% of normal – and 36.9 IU/dL at 18 months, about 37% of normal. There’s been no sign so far of patients developing inhibitors against the infusion.

Adverse events were common but largely mild and included headache and influenza-like illness, both in 13% of subjects. Nine patients needed steroids for liver enzyme elevations.

The trial was temporarily halted due to a case of liver cancer, but it was ultimately deemed not to be related to treatment, based on molecular tumor characterization and vector integration analysis. A death in the trial was also not considered treatment related.

Other gene therapies are in the pipeline for hemophilia, including valoctocogene roxaparvovec (Roctavian, BioMarin) for hemophilia A. FDA’s approval decision is expected in March 2023.

This article was updated 11/23/22.

Correction, 11/23/22: The brand name Hemgenix was misstated in an earlier version of this article.

A drug used in the treatment of relapsed/refractory multiple myeloma (RRMM) is in the process of being pulled off the U.S. market by its manufacturer.

The drug is belantamab mafodotin-blmf (Blenrep), an antibody drug conjugate that targets B-cell maturation antigen (BCMA).

The manufacturer, GSK, announced that it has started the process of withdrawing this drug from the market at the request of the U.S. Food and Drug Administration (FDA).

This request follows disappointing results from a large confirmatory trial, known as DREAMM-3, in which the drug failed to meet the primary endpoint of showing an improvement in progression-free survival (PFS).

The company was obliged to carry out this confirmatory trial after the FDA granted an accelerated approval for the drug in August 2020.

The accelerated approval was based on response data, and it was dependent on later trials’ confirming a clinical benefit. In this case, those trials did not confirm a clinical benefit.

“We respect the Agency’s approach to the accelerated approval regulations and associated process,” commented the GSK Chief Medical Officer Sabine Luik.

The company will continue to “work with the U.S. FDA on a path forward for this important treatment option for patients with multiple myeloma.”

Further clinical trials in the DREAMM program are still underway. Results from the DREAMM-7 and DREAMM-8 trials are expected in early 2023.

The company had high hopes for the drug when it was launched. At that time, belanatamab mafodotin-blmf was the only drug on the market that targeted BCMA, and so it was the first drug in its class.

However, it is no longer unique. In the 2 years that it has been available, several other products that target BCMA have been launched for use in the treatment of multiple myeloma. These include the two chimeric antigen receptor T-cell products, idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti), as well as the bispecific antibody teclistamab (Tecvayli).
 

For relapsed/refractory disease

Belantamab mafodotin-blmf was approved for use in patients with RRMM who had already undergone treatment with one of the three major classes of drugs, namely, an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.

Patients who are currently taking the drug and would like to continue doing so will have the option to enroll in a compassionate use program to retain their access to treatment, the company said.

“GSK continues to believe, based on the totality of data available from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) development program, that the benefit-risk profile of belantamab mafodotin remains favorable in this hard-to-treat RRMM patient population. Patients responding to belantamab mafodotin experienced durable clinical benefit, and safety remains consistent with the known safety profile,” the company said.
 

Details of DREAMM-3 results

DREAMM-3 was a phase 3 trial that compared single-agent belantamab mafodotin to pomalidomide (Pomalyst) in combination with low-dose dexamethasone (PomDex) for patients with RRMM.

The results for the primary endpoint of PFS did not reach statistical significance: median PFS was 11.2 vs. 7 months with PomDex (hazard ratio, 1.03; 95% confidence interval, 0.72-1.47).

At the time of the primary analysis, the overall survival (OS) data had only achieved 37.5% overall maturity. The median OS was 21.2 vs. 21.1 months with PomDex (HR, 1.14; 95% CI, 0.77-1.68).

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

A drug used in the treatment of relapsed/refractory multiple myeloma (RRMM) is in the process of being pulled off the U.S. market by its manufacturer.

The drug is belantamab mafodotin-blmf (Blenrep), an antibody drug conjugate that targets B-cell maturation antigen (BCMA).

The manufacturer, GSK, announced that it has started the process of withdrawing this drug from the market at the request of the U.S. Food and Drug Administration (FDA).

This request follows disappointing results from a large confirmatory trial, known as DREAMM-3, in which the drug failed to meet the primary endpoint of showing an improvement in progression-free survival (PFS).

The company was obliged to carry out this confirmatory trial after the FDA granted an accelerated approval for the drug in August 2020.

The accelerated approval was based on response data, and it was dependent on later trials’ confirming a clinical benefit. In this case, those trials did not confirm a clinical benefit.

“We respect the Agency’s approach to the accelerated approval regulations and associated process,” commented the GSK Chief Medical Officer Sabine Luik.

The company will continue to “work with the U.S. FDA on a path forward for this important treatment option for patients with multiple myeloma.”

Further clinical trials in the DREAMM program are still underway. Results from the DREAMM-7 and DREAMM-8 trials are expected in early 2023.

The company had high hopes for the drug when it was launched. At that time, belanatamab mafodotin-blmf was the only drug on the market that targeted BCMA, and so it was the first drug in its class.

However, it is no longer unique. In the 2 years that it has been available, several other products that target BCMA have been launched for use in the treatment of multiple myeloma. These include the two chimeric antigen receptor T-cell products, idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti), as well as the bispecific antibody teclistamab (Tecvayli).
 

For relapsed/refractory disease

Belantamab mafodotin-blmf was approved for use in patients with RRMM who had already undergone treatment with one of the three major classes of drugs, namely, an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.

Patients who are currently taking the drug and would like to continue doing so will have the option to enroll in a compassionate use program to retain their access to treatment, the company said.

“GSK continues to believe, based on the totality of data available from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) development program, that the benefit-risk profile of belantamab mafodotin remains favorable in this hard-to-treat RRMM patient population. Patients responding to belantamab mafodotin experienced durable clinical benefit, and safety remains consistent with the known safety profile,” the company said.
 

Details of DREAMM-3 results

DREAMM-3 was a phase 3 trial that compared single-agent belantamab mafodotin to pomalidomide (Pomalyst) in combination with low-dose dexamethasone (PomDex) for patients with RRMM.

The results for the primary endpoint of PFS did not reach statistical significance: median PFS was 11.2 vs. 7 months with PomDex (hazard ratio, 1.03; 95% confidence interval, 0.72-1.47).

At the time of the primary analysis, the overall survival (OS) data had only achieved 37.5% overall maturity. The median OS was 21.2 vs. 21.1 months with PomDex (HR, 1.14; 95% CI, 0.77-1.68).

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

A drug used in the treatment of relapsed/refractory multiple myeloma (RRMM) is in the process of being pulled off the U.S. market by its manufacturer.

The drug is belantamab mafodotin-blmf (Blenrep), an antibody drug conjugate that targets B-cell maturation antigen (BCMA).

The manufacturer, GSK, announced that it has started the process of withdrawing this drug from the market at the request of the U.S. Food and Drug Administration (FDA).

This request follows disappointing results from a large confirmatory trial, known as DREAMM-3, in which the drug failed to meet the primary endpoint of showing an improvement in progression-free survival (PFS).

The company was obliged to carry out this confirmatory trial after the FDA granted an accelerated approval for the drug in August 2020.

The accelerated approval was based on response data, and it was dependent on later trials’ confirming a clinical benefit. In this case, those trials did not confirm a clinical benefit.

“We respect the Agency’s approach to the accelerated approval regulations and associated process,” commented the GSK Chief Medical Officer Sabine Luik.

The company will continue to “work with the U.S. FDA on a path forward for this important treatment option for patients with multiple myeloma.”

Further clinical trials in the DREAMM program are still underway. Results from the DREAMM-7 and DREAMM-8 trials are expected in early 2023.

The company had high hopes for the drug when it was launched. At that time, belanatamab mafodotin-blmf was the only drug on the market that targeted BCMA, and so it was the first drug in its class.

However, it is no longer unique. In the 2 years that it has been available, several other products that target BCMA have been launched for use in the treatment of multiple myeloma. These include the two chimeric antigen receptor T-cell products, idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti), as well as the bispecific antibody teclistamab (Tecvayli).
 

For relapsed/refractory disease

Belantamab mafodotin-blmf was approved for use in patients with RRMM who had already undergone treatment with one of the three major classes of drugs, namely, an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.

Patients who are currently taking the drug and would like to continue doing so will have the option to enroll in a compassionate use program to retain their access to treatment, the company said.

“GSK continues to believe, based on the totality of data available from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) development program, that the benefit-risk profile of belantamab mafodotin remains favorable in this hard-to-treat RRMM patient population. Patients responding to belantamab mafodotin experienced durable clinical benefit, and safety remains consistent with the known safety profile,” the company said.
 

Details of DREAMM-3 results

DREAMM-3 was a phase 3 trial that compared single-agent belantamab mafodotin to pomalidomide (Pomalyst) in combination with low-dose dexamethasone (PomDex) for patients with RRMM.

The results for the primary endpoint of PFS did not reach statistical significance: median PFS was 11.2 vs. 7 months with PomDex (hazard ratio, 1.03; 95% confidence interval, 0.72-1.47).

At the time of the primary analysis, the overall survival (OS) data had only achieved 37.5% overall maturity. The median OS was 21.2 vs. 21.1 months with PomDex (HR, 1.14; 95% CI, 0.77-1.68).

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

Numerous species of fungi exist in cancer cells and differ by tumor type, according to findings from a large study of multiple sample types across 35 different cancers.

The investigators characterized the cancer mycobiome within 17,401 tissue, blood, and plasma samples from four international cohorts, revealing new information about fungi distribution, association with immune cells, and potential prognostic value.

Fungi were detected in all cancer types studied and were often intracellular, reported Lian Narunsky-Haziza, PhD, of Weizmann Institute of Science, Rehovot, Israel, and colleagues.

Additionally, multiple fungal-bacterial-immune ecologies were detected across tumors, and intratumoral fungi stratified clinical outcomes, including immunotherapy response, they noted. Also, cell-free fungal DNA diagnosed healthy and cancer patients in early-stage disease.

The findings, published online in the journal Cell, have potential implications for cancer detection, diagnosis, and treatment, the researchers suggested.

The existence of fungi in most human cancers “is both a surprise and to be expected,” study coauthor Rob Knight, PhD, a professor at the University of California, San Diego, stated in a press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”

Exploration of the associations between cancer and microbes are nothing new, but cancer-associated fungi have rarely been examined, the authors noted.

The findings from this pan-cancer analysis, which suggested “prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers,” complement current “understanding of the interaction between cancer cells and the bacteria that exist in tumors alongside fungi, bacteria that have been shown to affect cancer growth, metastasis, and response to therapy,” they explained.

Of note, the study revealed multiple correlations between the presence of specific fungi in tumors and conditions related to treatment. For example, patients with breast cancer whose tumors contained Malassezia globosa – a fungus found naturally on the skin – had a much lower survival rate than those whose tumors did not contain the fungus. Furthermore, specific fungi were more prevalent in breast tumors from older vs. younger patients, in lung tumors of smokers vs. nonsmokers, and in melanoma tumors that responded to immunotherapy vs. those that did not respond.

These findings suggest that fungal activity is “a new and emerging hallmark of cancer,” stated study coleader Ravid Straussman, PhD, of the Weizmann molecular cell biology department. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’ ”

Unique relationships observed between fungi and bacteria – for example, tumors that contain Aspergillus fungi tended to have specific bacteria in them, whereas tumors that contain Malassezia fungi tended to have other bacteria in them – may have implications for treatment, as they correlated with both tumor immunity and patient survival, according to the authors.

“This study sheds new light on the complex biological environment within tumors, and future research will reveal how fungi affect cancerous growth,” said coauthor Yitzhak Pilpel, PhD, a principal investigator at the Weizmann molecular genetics department. “The fact that fungi can be found not only in cancer cells but also in immune cells implies that, in the future, we’ll probably find that fungi have some effect not only on the cancer cells but also on immune cells and their activity.”

A further finding related to the presence of fungal and bacterial DNA in human blood further suggests that measuring microbial DNA in the blood could lead to early detection of cancer, the authors noted.

Dr. Straussman’s research is supported by the Swiss Society Institute for Cancer Prevention Research, the Fabricant-Morse Families Research Fund for Humanity, the Dr. Chantal d’Adesky Scheinberg Research Fund, and the Dr. Dvora and Haim Teitelbaum Endowment Fund.
 

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

Numerous species of fungi exist in cancer cells and differ by tumor type, according to findings from a large study of multiple sample types across 35 different cancers.

The investigators characterized the cancer mycobiome within 17,401 tissue, blood, and plasma samples from four international cohorts, revealing new information about fungi distribution, association with immune cells, and potential prognostic value.

Fungi were detected in all cancer types studied and were often intracellular, reported Lian Narunsky-Haziza, PhD, of Weizmann Institute of Science, Rehovot, Israel, and colleagues.

Additionally, multiple fungal-bacterial-immune ecologies were detected across tumors, and intratumoral fungi stratified clinical outcomes, including immunotherapy response, they noted. Also, cell-free fungal DNA diagnosed healthy and cancer patients in early-stage disease.

The findings, published online in the journal Cell, have potential implications for cancer detection, diagnosis, and treatment, the researchers suggested.

The existence of fungi in most human cancers “is both a surprise and to be expected,” study coauthor Rob Knight, PhD, a professor at the University of California, San Diego, stated in a press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”

Exploration of the associations between cancer and microbes are nothing new, but cancer-associated fungi have rarely been examined, the authors noted.

The findings from this pan-cancer analysis, which suggested “prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers,” complement current “understanding of the interaction between cancer cells and the bacteria that exist in tumors alongside fungi, bacteria that have been shown to affect cancer growth, metastasis, and response to therapy,” they explained.

Of note, the study revealed multiple correlations between the presence of specific fungi in tumors and conditions related to treatment. For example, patients with breast cancer whose tumors contained Malassezia globosa – a fungus found naturally on the skin – had a much lower survival rate than those whose tumors did not contain the fungus. Furthermore, specific fungi were more prevalent in breast tumors from older vs. younger patients, in lung tumors of smokers vs. nonsmokers, and in melanoma tumors that responded to immunotherapy vs. those that did not respond.

These findings suggest that fungal activity is “a new and emerging hallmark of cancer,” stated study coleader Ravid Straussman, PhD, of the Weizmann molecular cell biology department. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’ ”

Unique relationships observed between fungi and bacteria – for example, tumors that contain Aspergillus fungi tended to have specific bacteria in them, whereas tumors that contain Malassezia fungi tended to have other bacteria in them – may have implications for treatment, as they correlated with both tumor immunity and patient survival, according to the authors.

“This study sheds new light on the complex biological environment within tumors, and future research will reveal how fungi affect cancerous growth,” said coauthor Yitzhak Pilpel, PhD, a principal investigator at the Weizmann molecular genetics department. “The fact that fungi can be found not only in cancer cells but also in immune cells implies that, in the future, we’ll probably find that fungi have some effect not only on the cancer cells but also on immune cells and their activity.”

A further finding related to the presence of fungal and bacterial DNA in human blood further suggests that measuring microbial DNA in the blood could lead to early detection of cancer, the authors noted.

Dr. Straussman’s research is supported by the Swiss Society Institute for Cancer Prevention Research, the Fabricant-Morse Families Research Fund for Humanity, the Dr. Chantal d’Adesky Scheinberg Research Fund, and the Dr. Dvora and Haim Teitelbaum Endowment Fund.
 

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

Numerous species of fungi exist in cancer cells and differ by tumor type, according to findings from a large study of multiple sample types across 35 different cancers.

The investigators characterized the cancer mycobiome within 17,401 tissue, blood, and plasma samples from four international cohorts, revealing new information about fungi distribution, association with immune cells, and potential prognostic value.

Fungi were detected in all cancer types studied and were often intracellular, reported Lian Narunsky-Haziza, PhD, of Weizmann Institute of Science, Rehovot, Israel, and colleagues.

Additionally, multiple fungal-bacterial-immune ecologies were detected across tumors, and intratumoral fungi stratified clinical outcomes, including immunotherapy response, they noted. Also, cell-free fungal DNA diagnosed healthy and cancer patients in early-stage disease.

The findings, published online in the journal Cell, have potential implications for cancer detection, diagnosis, and treatment, the researchers suggested.

The existence of fungi in most human cancers “is both a surprise and to be expected,” study coauthor Rob Knight, PhD, a professor at the University of California, San Diego, stated in a press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”

Exploration of the associations between cancer and microbes are nothing new, but cancer-associated fungi have rarely been examined, the authors noted.

The findings from this pan-cancer analysis, which suggested “prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers,” complement current “understanding of the interaction between cancer cells and the bacteria that exist in tumors alongside fungi, bacteria that have been shown to affect cancer growth, metastasis, and response to therapy,” they explained.

Of note, the study revealed multiple correlations between the presence of specific fungi in tumors and conditions related to treatment. For example, patients with breast cancer whose tumors contained Malassezia globosa – a fungus found naturally on the skin – had a much lower survival rate than those whose tumors did not contain the fungus. Furthermore, specific fungi were more prevalent in breast tumors from older vs. younger patients, in lung tumors of smokers vs. nonsmokers, and in melanoma tumors that responded to immunotherapy vs. those that did not respond.

These findings suggest that fungal activity is “a new and emerging hallmark of cancer,” stated study coleader Ravid Straussman, PhD, of the Weizmann molecular cell biology department. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’ ”

Unique relationships observed between fungi and bacteria – for example, tumors that contain Aspergillus fungi tended to have specific bacteria in them, whereas tumors that contain Malassezia fungi tended to have other bacteria in them – may have implications for treatment, as they correlated with both tumor immunity and patient survival, according to the authors.

“This study sheds new light on the complex biological environment within tumors, and future research will reveal how fungi affect cancerous growth,” said coauthor Yitzhak Pilpel, PhD, a principal investigator at the Weizmann molecular genetics department. “The fact that fungi can be found not only in cancer cells but also in immune cells implies that, in the future, we’ll probably find that fungi have some effect not only on the cancer cells but also on immune cells and their activity.”

A further finding related to the presence of fungal and bacterial DNA in human blood further suggests that measuring microbial DNA in the blood could lead to early detection of cancer, the authors noted.

Dr. Straussman’s research is supported by the Swiss Society Institute for Cancer Prevention Research, the Fabricant-Morse Families Research Fund for Humanity, the Dr. Chantal d’Adesky Scheinberg Research Fund, and the Dr. Dvora and Haim Teitelbaum Endowment Fund.
 

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

As many as 40% of patients with cancer develop hiccups – often unbeknownst to their oncologists. But even if recognized, hiccups may not be treated effectively, according to a national survey of cancer care clinicians.

When poorly controlled, persistent hiccups can affect a patient’s quality of life, with 40% of survey respondents considering chronic hiccups “much more” or “somewhat more” severe than nausea and vomiting.

Overall, the findings indicate that patients with cancer who develop persistent hiccups are “truly suffering,” the authors wrote.

The survey results were published online recently in the American Journal of Hospice and Palliative Medicine.

Hiccups may simply be a nuisance for most, but these spasms can become problematic for patients with cancer, leading to sleep deprivation, fatigue, aspiration pneumonia, compromised food intake, weight loss, pain, and even death.

Hiccups can develop when the nerve that controls the diaphragm becomes irritated, which can be triggered by certain chemotherapy drugs.

Yet few studies have focused on hiccups in patients with cancer and none, until now, has sought the perspectives of cancer care clinicians.

Aminah Jatoi, MD, medical oncologist with the Mayo Clinic in Rochester, Minn., and two Mayo colleagues developed a survey, alongside MeterHealth, which this news organization distributed to clinicians with an interest in cancer care.

The survey gauged clinicians’ awareness or lack of awareness about clinically significant hiccups as well as treatments for hiccups and whether they consider hiccups an unmet palliative need.

A total of 684 clinicians completed two eligibility screening questions, which required them to have cared for more than 10 patients with cancer in the past 6 months with clinically significant hiccups (defined as hiccups that lasted more than 48 hours or occurred from cancer or cancer care).

Among 113 eligible health care professionals, 90 completed the survey: 42 physicians, 29 nurses, 15 nurse practitioners, and 4 physician assistants.

The survey revealed three key issues.

The first is that hiccups appear to be an underrecognized issue.

Among health care professionals who answered the eligibility screening questions, fewer than 20% reported caring for more than 10 patients with cancer in the past 6 months who had persistent hiccups. Most of these clinicians reported caring for more than 1,000 patients per year.

Given that 15%-40% of patients with cancer report hiccups, this finding suggests that hiccups are not widely recognized by health care professionals.

Second: The survey data showed that hiccups often increase patients’ anxiety, fatigue, and sleep problems and can decrease productivity at work or school.

In fact, when comparing hiccups to nausea and vomiting – sometimes described as one of the most severe side effects of cancer care – 40% of respondents rated hiccups as “much more” or “somewhat more” severe than nausea and vomiting for their patients and 38% rated the severity of the two issues as “about the same.”

Finally, even when hiccups are recognized and treated, about 20% of respondents said that current therapies are not very effective, and more treatment options are needed.

Among the survey respondents, the most frequently prescribed medications for chronic hiccups were the antipsychotic chlorpromazine, the muscle relaxant baclofen (Lioresal), the antiemetic metoclopramide (Metozolv ODT, Reglan), and the anticonvulsants gabapentin (Neurontin) and carbamazepine (Tegretol).

Survey respondents who provided comments about current treatments for hiccups highlighted a range of challenges. One respondent said, “When current therapies do not work, it can be very demoralizing to our patients.”  Another said, “I feel like it is a gamble whether treatment for hiccups will work or not.”

Still another felt that while current treatments work “quite well to halt hiccups,” they come with side effects which can be “quite severe.”

These results “clearly point to the unmet needs of hiccups in patients with cancer and should prompt more research aimed at generating more palliative options,” the authors said.

This research had no commercial funding. MeterHealth reviewed the manuscript and provided input on the accuracy of methods and results. Dr. Jatoi reports serving on an advisory board for MeterHealth (honoraria to institution).

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

As many as 40% of patients with cancer develop hiccups – often unbeknownst to their oncologists. But even if recognized, hiccups may not be treated effectively, according to a national survey of cancer care clinicians.

When poorly controlled, persistent hiccups can affect a patient’s quality of life, with 40% of survey respondents considering chronic hiccups “much more” or “somewhat more” severe than nausea and vomiting.

Overall, the findings indicate that patients with cancer who develop persistent hiccups are “truly suffering,” the authors wrote.

The survey results were published online recently in the American Journal of Hospice and Palliative Medicine.

Hiccups may simply be a nuisance for most, but these spasms can become problematic for patients with cancer, leading to sleep deprivation, fatigue, aspiration pneumonia, compromised food intake, weight loss, pain, and even death.

Hiccups can develop when the nerve that controls the diaphragm becomes irritated, which can be triggered by certain chemotherapy drugs.

Yet few studies have focused on hiccups in patients with cancer and none, until now, has sought the perspectives of cancer care clinicians.

Aminah Jatoi, MD, medical oncologist with the Mayo Clinic in Rochester, Minn., and two Mayo colleagues developed a survey, alongside MeterHealth, which this news organization distributed to clinicians with an interest in cancer care.

The survey gauged clinicians’ awareness or lack of awareness about clinically significant hiccups as well as treatments for hiccups and whether they consider hiccups an unmet palliative need.

A total of 684 clinicians completed two eligibility screening questions, which required them to have cared for more than 10 patients with cancer in the past 6 months with clinically significant hiccups (defined as hiccups that lasted more than 48 hours or occurred from cancer or cancer care).

Among 113 eligible health care professionals, 90 completed the survey: 42 physicians, 29 nurses, 15 nurse practitioners, and 4 physician assistants.

The survey revealed three key issues.

The first is that hiccups appear to be an underrecognized issue.

Among health care professionals who answered the eligibility screening questions, fewer than 20% reported caring for more than 10 patients with cancer in the past 6 months who had persistent hiccups. Most of these clinicians reported caring for more than 1,000 patients per year.

Given that 15%-40% of patients with cancer report hiccups, this finding suggests that hiccups are not widely recognized by health care professionals.

Second: The survey data showed that hiccups often increase patients’ anxiety, fatigue, and sleep problems and can decrease productivity at work or school.

In fact, when comparing hiccups to nausea and vomiting – sometimes described as one of the most severe side effects of cancer care – 40% of respondents rated hiccups as “much more” or “somewhat more” severe than nausea and vomiting for their patients and 38% rated the severity of the two issues as “about the same.”

Finally, even when hiccups are recognized and treated, about 20% of respondents said that current therapies are not very effective, and more treatment options are needed.

Among the survey respondents, the most frequently prescribed medications for chronic hiccups were the antipsychotic chlorpromazine, the muscle relaxant baclofen (Lioresal), the antiemetic metoclopramide (Metozolv ODT, Reglan), and the anticonvulsants gabapentin (Neurontin) and carbamazepine (Tegretol).

Survey respondents who provided comments about current treatments for hiccups highlighted a range of challenges. One respondent said, “When current therapies do not work, it can be very demoralizing to our patients.”  Another said, “I feel like it is a gamble whether treatment for hiccups will work or not.”

Still another felt that while current treatments work “quite well to halt hiccups,” they come with side effects which can be “quite severe.”

These results “clearly point to the unmet needs of hiccups in patients with cancer and should prompt more research aimed at generating more palliative options,” the authors said.

This research had no commercial funding. MeterHealth reviewed the manuscript and provided input on the accuracy of methods and results. Dr. Jatoi reports serving on an advisory board for MeterHealth (honoraria to institution).

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

As many as 40% of patients with cancer develop hiccups – often unbeknownst to their oncologists. But even if recognized, hiccups may not be treated effectively, according to a national survey of cancer care clinicians.

When poorly controlled, persistent hiccups can affect a patient’s quality of life, with 40% of survey respondents considering chronic hiccups “much more” or “somewhat more” severe than nausea and vomiting.

Overall, the findings indicate that patients with cancer who develop persistent hiccups are “truly suffering,” the authors wrote.

The survey results were published online recently in the American Journal of Hospice and Palliative Medicine.

Hiccups may simply be a nuisance for most, but these spasms can become problematic for patients with cancer, leading to sleep deprivation, fatigue, aspiration pneumonia, compromised food intake, weight loss, pain, and even death.

Hiccups can develop when the nerve that controls the diaphragm becomes irritated, which can be triggered by certain chemotherapy drugs.

Yet few studies have focused on hiccups in patients with cancer and none, until now, has sought the perspectives of cancer care clinicians.

Aminah Jatoi, MD, medical oncologist with the Mayo Clinic in Rochester, Minn., and two Mayo colleagues developed a survey, alongside MeterHealth, which this news organization distributed to clinicians with an interest in cancer care.

The survey gauged clinicians’ awareness or lack of awareness about clinically significant hiccups as well as treatments for hiccups and whether they consider hiccups an unmet palliative need.

A total of 684 clinicians completed two eligibility screening questions, which required them to have cared for more than 10 patients with cancer in the past 6 months with clinically significant hiccups (defined as hiccups that lasted more than 48 hours or occurred from cancer or cancer care).

Among 113 eligible health care professionals, 90 completed the survey: 42 physicians, 29 nurses, 15 nurse practitioners, and 4 physician assistants.

The survey revealed three key issues.

The first is that hiccups appear to be an underrecognized issue.

Among health care professionals who answered the eligibility screening questions, fewer than 20% reported caring for more than 10 patients with cancer in the past 6 months who had persistent hiccups. Most of these clinicians reported caring for more than 1,000 patients per year.

Given that 15%-40% of patients with cancer report hiccups, this finding suggests that hiccups are not widely recognized by health care professionals.

Second: The survey data showed that hiccups often increase patients’ anxiety, fatigue, and sleep problems and can decrease productivity at work or school.

In fact, when comparing hiccups to nausea and vomiting – sometimes described as one of the most severe side effects of cancer care – 40% of respondents rated hiccups as “much more” or “somewhat more” severe than nausea and vomiting for their patients and 38% rated the severity of the two issues as “about the same.”

Finally, even when hiccups are recognized and treated, about 20% of respondents said that current therapies are not very effective, and more treatment options are needed.

Among the survey respondents, the most frequently prescribed medications for chronic hiccups were the antipsychotic chlorpromazine, the muscle relaxant baclofen (Lioresal), the antiemetic metoclopramide (Metozolv ODT, Reglan), and the anticonvulsants gabapentin (Neurontin) and carbamazepine (Tegretol).

Survey respondents who provided comments about current treatments for hiccups highlighted a range of challenges. One respondent said, “When current therapies do not work, it can be very demoralizing to our patients.”  Another said, “I feel like it is a gamble whether treatment for hiccups will work or not.”

Still another felt that while current treatments work “quite well to halt hiccups,” they come with side effects which can be “quite severe.”

These results “clearly point to the unmet needs of hiccups in patients with cancer and should prompt more research aimed at generating more palliative options,” the authors said.

This research had no commercial funding. MeterHealth reviewed the manuscript and provided input on the accuracy of methods and results. Dr. Jatoi reports serving on an advisory board for MeterHealth (honoraria to institution).

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

An epidemiological analysis using genetic data shows that having babies protects women from endometrial cancer.

Compared with having no children, the risk reduction for endometrial cancer was 21% with having one child, 38% with having two, and 51% with having three, Gunn-Helen Moen, MSc, PhD, a research fellow at the University of Queensland Institute for Molecular Bioscience in St. Lucia, Australia, and the senior author of the study, said in an email.

In the United States, the prevalence of endometrial cancer is 25.7 per 100,000 women per year, with a lifetime risk of 2.8%.

Multiple observational studies have linked giving birth to risk of endometrial cancer. For the new study, Dr. Moen and her team assessed various risk factors related to ovulation and reproductive function using Mendelian randomization, an epidemiological technique that deploys genetic variants to detect cause-and-effect relationships between potentially modifiable risk factors and health outcomes in observational data.

The researcher published their findings in BMC Medicine.
 

Leverage genetic data

The study used detailed genetic and health data from the UK Biobank, a databank with more than half a million participants. Genetic variants related to some of the risk factors were used to assess whether the variants make people more likely to develop endometrial cancer.

Genomewide significant single-nucleotide polymorphisms (SNPs) related to number of live births, age at menopause and menarche, and body mass index (BMI) had been identified in previous studies, the researchers reported. They conducted genomewide association analyses of the databank to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

The MR analysis showed a potential causal effect for the number of live births (inverse variance–weighted odds ratio, 0.537) and number of years ovulating (IVW OR, 1.051), in addition to known risk factors of BMI, age at menarche, and age at menopause.

A further multivariable MR analysis showed that number of births had a negative causal effect on endometrial cancer risk (OR, 0.783), independent of the causal effect of known risk factors such as BMI, age at menarche and age at menopause.

Reported limitations included being unable to perform MR analyses on some factors, such as oral contraceptive use, because of a lack of valid genetic instruments. The researchers could not perform an age adjustment at diagnosis because of a lack of data.

In addition, the genetic data came exclusively from White women of European ancestry.
 

‘A personal choice’

Other investigators have hypothesized that the protective effect of childbirth may be caused by shedding of malignant and premalignant endometrial cells during and after childbirth and exposure to high levels of progesterone in late stages of pregnancy, the research team noted.

Dr. Moen said, based on the results, physicians might consider number of childbirths in assessing a patient’s risk of endometrial cancer.

However, Britton Trabert, MSPH, MS, PhD, an epidemiologist and assistant professor of obstetrics and gynecology at the University of Utah, Salt Lake City, said it’s unlikely the findings will affect clinical practice given that they “largely replicate well-characterized endometrial cancer risk associations.”

“Pregnancy and childbirth are a personal choice and is not largely regarded as a modifiable factor for cancer prevention,” said Dr. Trabert, who was not involved in the study.

The study’s investigators reported funding from the governments of Australia, Norway and the United Kingdom and the British Heart Foundation. No financial conflicts of interest were reported. Dr. Trabert reported no relevant financial interests.

An epidemiological analysis using genetic data shows that having babies protects women from endometrial cancer.

Compared with having no children, the risk reduction for endometrial cancer was 21% with having one child, 38% with having two, and 51% with having three, Gunn-Helen Moen, MSc, PhD, a research fellow at the University of Queensland Institute for Molecular Bioscience in St. Lucia, Australia, and the senior author of the study, said in an email.

In the United States, the prevalence of endometrial cancer is 25.7 per 100,000 women per year, with a lifetime risk of 2.8%.

Multiple observational studies have linked giving birth to risk of endometrial cancer. For the new study, Dr. Moen and her team assessed various risk factors related to ovulation and reproductive function using Mendelian randomization, an epidemiological technique that deploys genetic variants to detect cause-and-effect relationships between potentially modifiable risk factors and health outcomes in observational data.

The researcher published their findings in BMC Medicine.
 

Leverage genetic data

The study used detailed genetic and health data from the UK Biobank, a databank with more than half a million participants. Genetic variants related to some of the risk factors were used to assess whether the variants make people more likely to develop endometrial cancer.

Genomewide significant single-nucleotide polymorphisms (SNPs) related to number of live births, age at menopause and menarche, and body mass index (BMI) had been identified in previous studies, the researchers reported. They conducted genomewide association analyses of the databank to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

The MR analysis showed a potential causal effect for the number of live births (inverse variance–weighted odds ratio, 0.537) and number of years ovulating (IVW OR, 1.051), in addition to known risk factors of BMI, age at menarche, and age at menopause.

A further multivariable MR analysis showed that number of births had a negative causal effect on endometrial cancer risk (OR, 0.783), independent of the causal effect of known risk factors such as BMI, age at menarche and age at menopause.

Reported limitations included being unable to perform MR analyses on some factors, such as oral contraceptive use, because of a lack of valid genetic instruments. The researchers could not perform an age adjustment at diagnosis because of a lack of data.

In addition, the genetic data came exclusively from White women of European ancestry.
 

‘A personal choice’

Other investigators have hypothesized that the protective effect of childbirth may be caused by shedding of malignant and premalignant endometrial cells during and after childbirth and exposure to high levels of progesterone in late stages of pregnancy, the research team noted.

Dr. Moen said, based on the results, physicians might consider number of childbirths in assessing a patient’s risk of endometrial cancer.

However, Britton Trabert, MSPH, MS, PhD, an epidemiologist and assistant professor of obstetrics and gynecology at the University of Utah, Salt Lake City, said it’s unlikely the findings will affect clinical practice given that they “largely replicate well-characterized endometrial cancer risk associations.”

“Pregnancy and childbirth are a personal choice and is not largely regarded as a modifiable factor for cancer prevention,” said Dr. Trabert, who was not involved in the study.

The study’s investigators reported funding from the governments of Australia, Norway and the United Kingdom and the British Heart Foundation. No financial conflicts of interest were reported. Dr. Trabert reported no relevant financial interests.

An epidemiological analysis using genetic data shows that having babies protects women from endometrial cancer.

Compared with having no children, the risk reduction for endometrial cancer was 21% with having one child, 38% with having two, and 51% with having three, Gunn-Helen Moen, MSc, PhD, a research fellow at the University of Queensland Institute for Molecular Bioscience in St. Lucia, Australia, and the senior author of the study, said in an email.

In the United States, the prevalence of endometrial cancer is 25.7 per 100,000 women per year, with a lifetime risk of 2.8%.

Multiple observational studies have linked giving birth to risk of endometrial cancer. For the new study, Dr. Moen and her team assessed various risk factors related to ovulation and reproductive function using Mendelian randomization, an epidemiological technique that deploys genetic variants to detect cause-and-effect relationships between potentially modifiable risk factors and health outcomes in observational data.

The researcher published their findings in BMC Medicine.
 

Leverage genetic data

The study used detailed genetic and health data from the UK Biobank, a databank with more than half a million participants. Genetic variants related to some of the risk factors were used to assess whether the variants make people more likely to develop endometrial cancer.

Genomewide significant single-nucleotide polymorphisms (SNPs) related to number of live births, age at menopause and menarche, and body mass index (BMI) had been identified in previous studies, the researchers reported. They conducted genomewide association analyses of the databank to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth.

The MR analysis showed a potential causal effect for the number of live births (inverse variance–weighted odds ratio, 0.537) and number of years ovulating (IVW OR, 1.051), in addition to known risk factors of BMI, age at menarche, and age at menopause.

A further multivariable MR analysis showed that number of births had a negative causal effect on endometrial cancer risk (OR, 0.783), independent of the causal effect of known risk factors such as BMI, age at menarche and age at menopause.

Reported limitations included being unable to perform MR analyses on some factors, such as oral contraceptive use, because of a lack of valid genetic instruments. The researchers could not perform an age adjustment at diagnosis because of a lack of data.

In addition, the genetic data came exclusively from White women of European ancestry.
 

‘A personal choice’

Other investigators have hypothesized that the protective effect of childbirth may be caused by shedding of malignant and premalignant endometrial cells during and after childbirth and exposure to high levels of progesterone in late stages of pregnancy, the research team noted.

Dr. Moen said, based on the results, physicians might consider number of childbirths in assessing a patient’s risk of endometrial cancer.

However, Britton Trabert, MSPH, MS, PhD, an epidemiologist and assistant professor of obstetrics and gynecology at the University of Utah, Salt Lake City, said it’s unlikely the findings will affect clinical practice given that they “largely replicate well-characterized endometrial cancer risk associations.”

“Pregnancy and childbirth are a personal choice and is not largely regarded as a modifiable factor for cancer prevention,” said Dr. Trabert, who was not involved in the study.

The study’s investigators reported funding from the governments of Australia, Norway and the United Kingdom and the British Heart Foundation. No financial conflicts of interest were reported. Dr. Trabert reported no relevant financial interests.