Breast Cancer ICYMI

In women who have locally advanced breast cancer (LABC), staging defines the extent of the disease and guides therapy.

Researchers have found in the first large, randomized, controlled study on the subject that ¹⁸ F-labeled fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) finds more distant metastases and allows more accurate staging than usual staging, which is determined by a bone scan and computed tomography (CT) of the thorax/abdomen and pelvis.

Findings of the study, led by Ian S. Dayes, MD, MSc, with the department of oncology at McMaster University in Hamilton, Ont., were published online in the Journal of Clinical Oncology.
 

Scans indicate less aggressive treatment strategy

The authors of the new study wrote that women with LABC, who are at high risk of metastatic disease, have large tumors that “can involve the chest wall or skin, clinically fixed axillary lymph nodes, or infraclavicular, supraclavicular, or internal mammary lymphadenopathy.”

If staging does not detect metastases, treatment is centered on combined modality therapy with curative intent (neoadjuvant chemotherapy and surgery, followed by regional radiation). If metastases are found, the treatment goal changes to controlling the disease.

In this study, twice as many women saw their stage increase from stage IIB or III to stage IV when PET-CT was used instead of conventional staging, guiding their treatment toward less aggressive care to control, rather than attempt to cure, the disease.

The women included in this study had histological evidence of invasive ductal carcinoma of the breast and TNM stage III or IIb (T3N0, but not T2N1).
 

Methods and results

Between December 2016 and April 2022, consenting patients from six regional cancer centers in Ontario were randomly assigned to one of two groups: 184 patients were randomly assigned to whole-body PET-CT and 185 patients to conventional staging.

Overall, the authors wrote, 43 (23%) of PET-CT patients “were upstaged” to stage IV compared with 21 (11%) of the conventionally staged patients (relative risk, 2.4; 95% confidence interval [CI], 1.4-4.2, P = .002).

There were 33 patients in a subset with inflammatory breast cancer and, among them, 4 of 16 (25%) PET-CT patients were upstaged to stage IV compared with 4 of 17 (24%) conventionally staged patients.

In the patients who did not have inflammatory breast cancer, 39 of 168 (23%) PET-CT patients were upstaged compared with 17 (10%) of 168 in the conventionally staged group.

Journal of Clinical Oncology (JCO) Senior Deputy Editor Kathy D. Miller, MD, said that, “PET/CT staging identifies distant disease in more patients and changes goals of therapy. Further research is needed to determine the impact on patient outcome.”
 

Findings have already changed practice

Senior author, Mark Levine, MD, MSc, also with McMaster, said in an interview that the results of this study have already changed practice in Canada, and he expects the United States to follow suit.

Dr. Levine said the study is important “in terms of helping plan therapy and being very open and honest with patients as to their prognosis.”

The findings constitute level 1 evidence in favor of PET-CT. Already, in Canada, “because of the results of the study, people with stage III breast cancer can get a PET scan,” he said.

Dr. Levine said he expects this evidence also to clarify “wishy-washy” National Comprehensive Cancer Network guidelines on using PET scans for LABC in the United States when the guidelines are next updated.

“That will make it easier for payers in the United States,” he added.

Cost effectiveness, Dr. Levine said, is complicated, because on one hand PET scans are quite costly. But its use would lead to more women getting less aggressive and expensive therapy and surgery.

Dr. Levine noted that his team will be analyzing cost-effectiveness over the next year.
 

New questions with more in stage IV

In an editorial, Lajos Pusztai, MD, DPhil, scientific codirector of the breast center at Yale University in New Haven, Conn., noted that, “all good studies raise new questions” and this one is no exception.

He pointed out that the number of women with stage IV metastatic breast cancer (MBC) has been increasing over the past 2 decades because of more sensitive staging methods. At the same time the number of women with recurrent metastatic disease is decreasing, because adjuvant therapies have improved.
 

Findings highlight need for stage IV treatment studies

Dr. Pusztai noted that the patients who have de novo oligometastatic stage IV disease “are a unique subset among patients with MBC,” and the best treatment [for them] has not been established in randomized, controlled trials.

“Almost all randomized trials that targeted oligometastatic patients accrued mostly recurrent metastatic cancers; many included various cancer types, and none have tested the value of systemic multidrug regimens administered with curative intent,” he wrote.

If the health care systems adopt PET-CT for routine staging of locally advanced breast cancer, that will increase the diagnosis of de novo oligometastatic stage IV breast cancer, Dr. Pusztai said. That “underlines the importance of conducting studies for this unique subset of patients to establish level 1 evidence-based treatment strategies.”

Dr. Dayes has received honoraria from Verity Pharmaceuticals. One coauthor is employed by Point Biopharma. Other coauthors reported ties with AbbVie, Agendia, Genomic Health, InMode and Lutronic. Dr. Pusztai’s institution has received research funding from Merck, Genentech, Seagen, AstraZeneca, Bristol Myers Squibb, and Pfizer. He has received honoraria and travel expenses and has served in a consulting role for several pharmaceutical companies. Full disclosures are available on Open Payments.

In women who have locally advanced breast cancer (LABC), staging defines the extent of the disease and guides therapy.

Researchers have found in the first large, randomized, controlled study on the subject that ¹⁸ F-labeled fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) finds more distant metastases and allows more accurate staging than usual staging, which is determined by a bone scan and computed tomography (CT) of the thorax/abdomen and pelvis.

Findings of the study, led by Ian S. Dayes, MD, MSc, with the department of oncology at McMaster University in Hamilton, Ont., were published online in the Journal of Clinical Oncology.
 

Scans indicate less aggressive treatment strategy

The authors of the new study wrote that women with LABC, who are at high risk of metastatic disease, have large tumors that “can involve the chest wall or skin, clinically fixed axillary lymph nodes, or infraclavicular, supraclavicular, or internal mammary lymphadenopathy.”

If staging does not detect metastases, treatment is centered on combined modality therapy with curative intent (neoadjuvant chemotherapy and surgery, followed by regional radiation). If metastases are found, the treatment goal changes to controlling the disease.

In this study, twice as many women saw their stage increase from stage IIB or III to stage IV when PET-CT was used instead of conventional staging, guiding their treatment toward less aggressive care to control, rather than attempt to cure, the disease.

The women included in this study had histological evidence of invasive ductal carcinoma of the breast and TNM stage III or IIb (T3N0, but not T2N1).
 

Methods and results

Between December 2016 and April 2022, consenting patients from six regional cancer centers in Ontario were randomly assigned to one of two groups: 184 patients were randomly assigned to whole-body PET-CT and 185 patients to conventional staging.

Overall, the authors wrote, 43 (23%) of PET-CT patients “were upstaged” to stage IV compared with 21 (11%) of the conventionally staged patients (relative risk, 2.4; 95% confidence interval [CI], 1.4-4.2, P = .002).

There were 33 patients in a subset with inflammatory breast cancer and, among them, 4 of 16 (25%) PET-CT patients were upstaged to stage IV compared with 4 of 17 (24%) conventionally staged patients.

In the patients who did not have inflammatory breast cancer, 39 of 168 (23%) PET-CT patients were upstaged compared with 17 (10%) of 168 in the conventionally staged group.

Journal of Clinical Oncology (JCO) Senior Deputy Editor Kathy D. Miller, MD, said that, “PET/CT staging identifies distant disease in more patients and changes goals of therapy. Further research is needed to determine the impact on patient outcome.”
 

Findings have already changed practice

Senior author, Mark Levine, MD, MSc, also with McMaster, said in an interview that the results of this study have already changed practice in Canada, and he expects the United States to follow suit.

Dr. Levine said the study is important “in terms of helping plan therapy and being very open and honest with patients as to their prognosis.”

The findings constitute level 1 evidence in favor of PET-CT. Already, in Canada, “because of the results of the study, people with stage III breast cancer can get a PET scan,” he said.

Dr. Levine said he expects this evidence also to clarify “wishy-washy” National Comprehensive Cancer Network guidelines on using PET scans for LABC in the United States when the guidelines are next updated.

“That will make it easier for payers in the United States,” he added.

Cost effectiveness, Dr. Levine said, is complicated, because on one hand PET scans are quite costly. But its use would lead to more women getting less aggressive and expensive therapy and surgery.

Dr. Levine noted that his team will be analyzing cost-effectiveness over the next year.
 

New questions with more in stage IV

In an editorial, Lajos Pusztai, MD, DPhil, scientific codirector of the breast center at Yale University in New Haven, Conn., noted that, “all good studies raise new questions” and this one is no exception.

He pointed out that the number of women with stage IV metastatic breast cancer (MBC) has been increasing over the past 2 decades because of more sensitive staging methods. At the same time the number of women with recurrent metastatic disease is decreasing, because adjuvant therapies have improved.
 

Findings highlight need for stage IV treatment studies

Dr. Pusztai noted that the patients who have de novo oligometastatic stage IV disease “are a unique subset among patients with MBC,” and the best treatment [for them] has not been established in randomized, controlled trials.

“Almost all randomized trials that targeted oligometastatic patients accrued mostly recurrent metastatic cancers; many included various cancer types, and none have tested the value of systemic multidrug regimens administered with curative intent,” he wrote.

If the health care systems adopt PET-CT for routine staging of locally advanced breast cancer, that will increase the diagnosis of de novo oligometastatic stage IV breast cancer, Dr. Pusztai said. That “underlines the importance of conducting studies for this unique subset of patients to establish level 1 evidence-based treatment strategies.”

Dr. Dayes has received honoraria from Verity Pharmaceuticals. One coauthor is employed by Point Biopharma. Other coauthors reported ties with AbbVie, Agendia, Genomic Health, InMode and Lutronic. Dr. Pusztai’s institution has received research funding from Merck, Genentech, Seagen, AstraZeneca, Bristol Myers Squibb, and Pfizer. He has received honoraria and travel expenses and has served in a consulting role for several pharmaceutical companies. Full disclosures are available on Open Payments.

In women who have locally advanced breast cancer (LABC), staging defines the extent of the disease and guides therapy.

Researchers have found in the first large, randomized, controlled study on the subject that ¹⁸ F-labeled fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) finds more distant metastases and allows more accurate staging than usual staging, which is determined by a bone scan and computed tomography (CT) of the thorax/abdomen and pelvis.

Findings of the study, led by Ian S. Dayes, MD, MSc, with the department of oncology at McMaster University in Hamilton, Ont., were published online in the Journal of Clinical Oncology.
 

Scans indicate less aggressive treatment strategy

The authors of the new study wrote that women with LABC, who are at high risk of metastatic disease, have large tumors that “can involve the chest wall or skin, clinically fixed axillary lymph nodes, or infraclavicular, supraclavicular, or internal mammary lymphadenopathy.”

If staging does not detect metastases, treatment is centered on combined modality therapy with curative intent (neoadjuvant chemotherapy and surgery, followed by regional radiation). If metastases are found, the treatment goal changes to controlling the disease.

In this study, twice as many women saw their stage increase from stage IIB or III to stage IV when PET-CT was used instead of conventional staging, guiding their treatment toward less aggressive care to control, rather than attempt to cure, the disease.

The women included in this study had histological evidence of invasive ductal carcinoma of the breast and TNM stage III or IIb (T3N0, but not T2N1).
 

Methods and results

Between December 2016 and April 2022, consenting patients from six regional cancer centers in Ontario were randomly assigned to one of two groups: 184 patients were randomly assigned to whole-body PET-CT and 185 patients to conventional staging.

Overall, the authors wrote, 43 (23%) of PET-CT patients “were upstaged” to stage IV compared with 21 (11%) of the conventionally staged patients (relative risk, 2.4; 95% confidence interval [CI], 1.4-4.2, P = .002).

There were 33 patients in a subset with inflammatory breast cancer and, among them, 4 of 16 (25%) PET-CT patients were upstaged to stage IV compared with 4 of 17 (24%) conventionally staged patients.

In the patients who did not have inflammatory breast cancer, 39 of 168 (23%) PET-CT patients were upstaged compared with 17 (10%) of 168 in the conventionally staged group.

Journal of Clinical Oncology (JCO) Senior Deputy Editor Kathy D. Miller, MD, said that, “PET/CT staging identifies distant disease in more patients and changes goals of therapy. Further research is needed to determine the impact on patient outcome.”
 

Findings have already changed practice

Senior author, Mark Levine, MD, MSc, also with McMaster, said in an interview that the results of this study have already changed practice in Canada, and he expects the United States to follow suit.

Dr. Levine said the study is important “in terms of helping plan therapy and being very open and honest with patients as to their prognosis.”

The findings constitute level 1 evidence in favor of PET-CT. Already, in Canada, “because of the results of the study, people with stage III breast cancer can get a PET scan,” he said.

Dr. Levine said he expects this evidence also to clarify “wishy-washy” National Comprehensive Cancer Network guidelines on using PET scans for LABC in the United States when the guidelines are next updated.

“That will make it easier for payers in the United States,” he added.

Cost effectiveness, Dr. Levine said, is complicated, because on one hand PET scans are quite costly. But its use would lead to more women getting less aggressive and expensive therapy and surgery.

Dr. Levine noted that his team will be analyzing cost-effectiveness over the next year.
 

New questions with more in stage IV

In an editorial, Lajos Pusztai, MD, DPhil, scientific codirector of the breast center at Yale University in New Haven, Conn., noted that, “all good studies raise new questions” and this one is no exception.

He pointed out that the number of women with stage IV metastatic breast cancer (MBC) has been increasing over the past 2 decades because of more sensitive staging methods. At the same time the number of women with recurrent metastatic disease is decreasing, because adjuvant therapies have improved.
 

Findings highlight need for stage IV treatment studies

Dr. Pusztai noted that the patients who have de novo oligometastatic stage IV disease “are a unique subset among patients with MBC,” and the best treatment [for them] has not been established in randomized, controlled trials.

“Almost all randomized trials that targeted oligometastatic patients accrued mostly recurrent metastatic cancers; many included various cancer types, and none have tested the value of systemic multidrug regimens administered with curative intent,” he wrote.

If the health care systems adopt PET-CT for routine staging of locally advanced breast cancer, that will increase the diagnosis of de novo oligometastatic stage IV breast cancer, Dr. Pusztai said. That “underlines the importance of conducting studies for this unique subset of patients to establish level 1 evidence-based treatment strategies.”

Dr. Dayes has received honoraria from Verity Pharmaceuticals. One coauthor is employed by Point Biopharma. Other coauthors reported ties with AbbVie, Agendia, Genomic Health, InMode and Lutronic. Dr. Pusztai’s institution has received research funding from Merck, Genentech, Seagen, AstraZeneca, Bristol Myers Squibb, and Pfizer. He has received honoraria and travel expenses and has served in a consulting role for several pharmaceutical companies. Full disclosures are available on Open Payments.

After a median follow-up of 21.6 mo, the dalpiciclib group demonstrated a significantly longer median progression-free survival (PFS) compared with the placebo group (30.6 mo vs 18.2 mo; stratified hazard ratio [HR] 0.51; 95% CI 0.38-0.69; P < .0001). Overall, the dalpiciclib group demonstrated a manageable safety profile, although a higher percentage of grade 3/4 adverse events was noted with dalpiciclib than with placebo (90% vs 12%), as expected. Overall survival data for this CDK4/6 inhibitor are yet to come. These results suggest that dalpiciclib in combination with endocrine therapy is an alternative treatment for this group of patients, especially in countries where the traditionally approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are not available.

The optimal sequencing of endocrine therapy (ET) after progression on CDK4/6 inhibitor–based therapy remains a challenge. In the phase 2 MAINTAIN trial, 119 patients (all of whom had HR+/HER2- metastatic breast cancer and who progressed on ET and CDK4/6 inhibitors) were randomly assigned to receive a different ET (fulvestrant or exemestane) from the previous ET they had received plus either the CDK4/6 inhibitor ribociclib or placebo. In the study by Kalinksky and colleagues, at a median follow-up of 18.2 mo, a significant improvement in PFS was observed in the switched ET-plus-ribociclib group compared with the switched ET-plus-placebo group (HR 0.57; P = .006). The phase 2 MAINTAIN trial is the first randomized trial to show the benefit of a CDK4/6 inhibitor after progression on another CDK4/6 inhibitor. It is important to note that the majority of patients in the MAINTAIN study previously received palbociclib in the first-line setting, which in recent studies has been demonstrated to be inferior to other CDK4/6 inhibitors. Therefore, it is important to confirm whether this will hold true upon progression from ribociclib or abemaciclib in the first-line setting. In addition, more data are needed to compare this approach with other ET treatment options, such as phosphoinositide 3-kinases inhibitors and oral selective estrogen receptor degraders.

There are several options for adjuvant radiation therapy for early-stage breast cancer. A meta-analysis of 14 randomized controlled trials and six comparative observational studies assessed the efficacy of whole breast irradiation (WBI) compared with partial breast irradiation (PBI) in 17,234 adults with early-stage breast cancer. Results of this meta-analysis showed that PBI was not significantly different from WBI, with similar rates of ipsilateral breast recurrence  at 5 years (relative risk [RR] 1.34; 95% CI 0.83-2.18) and 10 years (RR 1.29; 95% CI 0.87-1.91), although patients undergoing PBI reported fewer acute adverse events  compared with patients undergoing WBI (incidence rate ratio [IRR] 0.53; 95% CI 0.31-0.92) and acute grade ≥2 adverse events (IRR 0.21; 95% CI 0.07-0.62). These findings support using PBI as the adjuvant radiotherapy modality for select patients with favorable-risk early-stage breast cancer.

Another meta-analysis looked at assessing the survival benefit of adding CDK4/6 inhibitors to standard ET in older patients with advanced breast cancer. The study included 10 trials with 1985 older patients with advanced ER+ breast cancer who received ET with or without CDK4/6 inhibitors. The findings showed that adding CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced the mortality risk by 21% (HR 0.79; 95% CI 0.69-0.91) and progression risk by 41% (HR 0.59; 95% CI 0.51-0.69) in older patients (age ≥ 65 years) with advanced breast cancer. Grade 3-4 neutropenia and diarrhea were similar in older patients. This study supports the use of CDK4/6 inhibitors as a reasonable treatment modality for older patients. More studies dedicated to the geriatric population are needed to help elaborate on the efficacy and tolerability of such agents in this population.

The phase 3 National Surgical Adjuvant Breast and Bowel Project B-42 (NSABP B-42) trial evaluated the role of extended letrozole therapy in postmenopausal breast cancer patients who were disease-free after 5 years of aromatase inhibitor–based therapy. The study included 3966 postmenopausal women with stage I-IIIA HR+ breast cancer who were randomly assigned to receive letrozole or placebo for 5 more years. After a median follow-up of 10.3 years, letrozole significantly improved disease-free survival (10-year absolute benefit 3.4%; HR 0.85; P = .01) compared with placebo, although there were no differences noted in overall survival between the groups (HR 0.97, P = .74). Furthermore, letrozole significantly reduced the breast cancer–free interval (HR 0.75, ,P = .003) and distant recurrence (HR 0.72, P = .01). There were no notable differences in toxicity, particularly rates of osteoporotic fractures and arterial thrombotic events, between the groups. Extended therapy with aromatase inhibitors beyond 5 years can be considered for select patients with early-stage breast cancer. Careful consideration of risks and benefits is needed to make these recommendations. 

After a median follow-up of 21.6 mo, the dalpiciclib group demonstrated a significantly longer median progression-free survival (PFS) compared with the placebo group (30.6 mo vs 18.2 mo; stratified hazard ratio [HR] 0.51; 95% CI 0.38-0.69; P < .0001). Overall, the dalpiciclib group demonstrated a manageable safety profile, although a higher percentage of grade 3/4 adverse events was noted with dalpiciclib than with placebo (90% vs 12%), as expected. Overall survival data for this CDK4/6 inhibitor are yet to come. These results suggest that dalpiciclib in combination with endocrine therapy is an alternative treatment for this group of patients, especially in countries where the traditionally approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are not available.

The optimal sequencing of endocrine therapy (ET) after progression on CDK4/6 inhibitor–based therapy remains a challenge. In the phase 2 MAINTAIN trial, 119 patients (all of whom had HR+/HER2- metastatic breast cancer and who progressed on ET and CDK4/6 inhibitors) were randomly assigned to receive a different ET (fulvestrant or exemestane) from the previous ET they had received plus either the CDK4/6 inhibitor ribociclib or placebo. In the study by Kalinksky and colleagues, at a median follow-up of 18.2 mo, a significant improvement in PFS was observed in the switched ET-plus-ribociclib group compared with the switched ET-plus-placebo group (HR 0.57; P = .006). The phase 2 MAINTAIN trial is the first randomized trial to show the benefit of a CDK4/6 inhibitor after progression on another CDK4/6 inhibitor. It is important to note that the majority of patients in the MAINTAIN study previously received palbociclib in the first-line setting, which in recent studies has been demonstrated to be inferior to other CDK4/6 inhibitors. Therefore, it is important to confirm whether this will hold true upon progression from ribociclib or abemaciclib in the first-line setting. In addition, more data are needed to compare this approach with other ET treatment options, such as phosphoinositide 3-kinases inhibitors and oral selective estrogen receptor degraders.

There are several options for adjuvant radiation therapy for early-stage breast cancer. A meta-analysis of 14 randomized controlled trials and six comparative observational studies assessed the efficacy of whole breast irradiation (WBI) compared with partial breast irradiation (PBI) in 17,234 adults with early-stage breast cancer. Results of this meta-analysis showed that PBI was not significantly different from WBI, with similar rates of ipsilateral breast recurrence  at 5 years (relative risk [RR] 1.34; 95% CI 0.83-2.18) and 10 years (RR 1.29; 95% CI 0.87-1.91), although patients undergoing PBI reported fewer acute adverse events  compared with patients undergoing WBI (incidence rate ratio [IRR] 0.53; 95% CI 0.31-0.92) and acute grade ≥2 adverse events (IRR 0.21; 95% CI 0.07-0.62). These findings support using PBI as the adjuvant radiotherapy modality for select patients with favorable-risk early-stage breast cancer.

Another meta-analysis looked at assessing the survival benefit of adding CDK4/6 inhibitors to standard ET in older patients with advanced breast cancer. The study included 10 trials with 1985 older patients with advanced ER+ breast cancer who received ET with or without CDK4/6 inhibitors. The findings showed that adding CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced the mortality risk by 21% (HR 0.79; 95% CI 0.69-0.91) and progression risk by 41% (HR 0.59; 95% CI 0.51-0.69) in older patients (age ≥ 65 years) with advanced breast cancer. Grade 3-4 neutropenia and diarrhea were similar in older patients. This study supports the use of CDK4/6 inhibitors as a reasonable treatment modality for older patients. More studies dedicated to the geriatric population are needed to help elaborate on the efficacy and tolerability of such agents in this population.

The phase 3 National Surgical Adjuvant Breast and Bowel Project B-42 (NSABP B-42) trial evaluated the role of extended letrozole therapy in postmenopausal breast cancer patients who were disease-free after 5 years of aromatase inhibitor–based therapy. The study included 3966 postmenopausal women with stage I-IIIA HR+ breast cancer who were randomly assigned to receive letrozole or placebo for 5 more years. After a median follow-up of 10.3 years, letrozole significantly improved disease-free survival (10-year absolute benefit 3.4%; HR 0.85; P = .01) compared with placebo, although there were no differences noted in overall survival between the groups (HR 0.97, P = .74). Furthermore, letrozole significantly reduced the breast cancer–free interval (HR 0.75, ,P = .003) and distant recurrence (HR 0.72, P = .01). There were no notable differences in toxicity, particularly rates of osteoporotic fractures and arterial thrombotic events, between the groups. Extended therapy with aromatase inhibitors beyond 5 years can be considered for select patients with early-stage breast cancer. Careful consideration of risks and benefits is needed to make these recommendations. 

After a median follow-up of 21.6 mo, the dalpiciclib group demonstrated a significantly longer median progression-free survival (PFS) compared with the placebo group (30.6 mo vs 18.2 mo; stratified hazard ratio [HR] 0.51; 95% CI 0.38-0.69; P < .0001). Overall, the dalpiciclib group demonstrated a manageable safety profile, although a higher percentage of grade 3/4 adverse events was noted with dalpiciclib than with placebo (90% vs 12%), as expected. Overall survival data for this CDK4/6 inhibitor are yet to come. These results suggest that dalpiciclib in combination with endocrine therapy is an alternative treatment for this group of patients, especially in countries where the traditionally approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) are not available.

The optimal sequencing of endocrine therapy (ET) after progression on CDK4/6 inhibitor–based therapy remains a challenge. In the phase 2 MAINTAIN trial, 119 patients (all of whom had HR+/HER2- metastatic breast cancer and who progressed on ET and CDK4/6 inhibitors) were randomly assigned to receive a different ET (fulvestrant or exemestane) from the previous ET they had received plus either the CDK4/6 inhibitor ribociclib or placebo. In the study by Kalinksky and colleagues, at a median follow-up of 18.2 mo, a significant improvement in PFS was observed in the switched ET-plus-ribociclib group compared with the switched ET-plus-placebo group (HR 0.57; P = .006). The phase 2 MAINTAIN trial is the first randomized trial to show the benefit of a CDK4/6 inhibitor after progression on another CDK4/6 inhibitor. It is important to note that the majority of patients in the MAINTAIN study previously received palbociclib in the first-line setting, which in recent studies has been demonstrated to be inferior to other CDK4/6 inhibitors. Therefore, it is important to confirm whether this will hold true upon progression from ribociclib or abemaciclib in the first-line setting. In addition, more data are needed to compare this approach with other ET treatment options, such as phosphoinositide 3-kinases inhibitors and oral selective estrogen receptor degraders.

There are several options for adjuvant radiation therapy for early-stage breast cancer. A meta-analysis of 14 randomized controlled trials and six comparative observational studies assessed the efficacy of whole breast irradiation (WBI) compared with partial breast irradiation (PBI) in 17,234 adults with early-stage breast cancer. Results of this meta-analysis showed that PBI was not significantly different from WBI, with similar rates of ipsilateral breast recurrence  at 5 years (relative risk [RR] 1.34; 95% CI 0.83-2.18) and 10 years (RR 1.29; 95% CI 0.87-1.91), although patients undergoing PBI reported fewer acute adverse events  compared with patients undergoing WBI (incidence rate ratio [IRR] 0.53; 95% CI 0.31-0.92) and acute grade ≥2 adverse events (IRR 0.21; 95% CI 0.07-0.62). These findings support using PBI as the adjuvant radiotherapy modality for select patients with favorable-risk early-stage breast cancer.

Another meta-analysis looked at assessing the survival benefit of adding CDK4/6 inhibitors to standard ET in older patients with advanced breast cancer. The study included 10 trials with 1985 older patients with advanced ER+ breast cancer who received ET with or without CDK4/6 inhibitors. The findings showed that adding CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced the mortality risk by 21% (HR 0.79; 95% CI 0.69-0.91) and progression risk by 41% (HR 0.59; 95% CI 0.51-0.69) in older patients (age ≥ 65 years) with advanced breast cancer. Grade 3-4 neutropenia and diarrhea were similar in older patients. This study supports the use of CDK4/6 inhibitors as a reasonable treatment modality for older patients. More studies dedicated to the geriatric population are needed to help elaborate on the efficacy and tolerability of such agents in this population.

The phase 3 National Surgical Adjuvant Breast and Bowel Project B-42 (NSABP B-42) trial evaluated the role of extended letrozole therapy in postmenopausal breast cancer patients who were disease-free after 5 years of aromatase inhibitor–based therapy. The study included 3966 postmenopausal women with stage I-IIIA HR+ breast cancer who were randomly assigned to receive letrozole or placebo for 5 more years. After a median follow-up of 10.3 years, letrozole significantly improved disease-free survival (10-year absolute benefit 3.4%; HR 0.85; P = .01) compared with placebo, although there were no differences noted in overall survival between the groups (HR 0.97, P = .74). Furthermore, letrozole significantly reduced the breast cancer–free interval (HR 0.75, ,P = .003) and distant recurrence (HR 0.72, P = .01). There were no notable differences in toxicity, particularly rates of osteoporotic fractures and arterial thrombotic events, between the groups. Extended therapy with aromatase inhibitors beyond 5 years can be considered for select patients with early-stage breast cancer. Careful consideration of risks and benefits is needed to make these recommendations. 

CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.

For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.

When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.

There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.

Researchers from the Alliance for Clinical Trials in Oncology explained how a multifaceted approach resulted in a 75% relative improvement in trial enrollment from 2014 to 2022, a period that included a pandemic-induced hiatus in clinical trials in general.

Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.

During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.

Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.

“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.

The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
 

Program to increase underrepresented patient accrual

The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.

“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.

“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
 

What works?

The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”

“I’m going to violate the rules of your question,” Dr. Paskett replied.

“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.

She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.

Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:

• Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
• Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
• Translation of informational materials for patients.
• Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
• Real-time monitoring of accrual demographics by the Alliance and at the trial site.
• Closing protocol enrollment to majority populations.
• Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.

The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.

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

CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.

For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.

When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.

There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.

Researchers from the Alliance for Clinical Trials in Oncology explained how a multifaceted approach resulted in a 75% relative improvement in trial enrollment from 2014 to 2022, a period that included a pandemic-induced hiatus in clinical trials in general.

Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.

During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.

Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.

“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.

The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
 

Program to increase underrepresented patient accrual

The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.

“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.

“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
 

What works?

The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”

“I’m going to violate the rules of your question,” Dr. Paskett replied.

“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.

She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.

Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:

• Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
• Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
• Translation of informational materials for patients.
• Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
• Real-time monitoring of accrual demographics by the Alliance and at the trial site.
• Closing protocol enrollment to majority populations.
• Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.

The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.

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

CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.

For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.

When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.

There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.

Researchers from the Alliance for Clinical Trials in Oncology explained how a multifaceted approach resulted in a 75% relative improvement in trial enrollment from 2014 to 2022, a period that included a pandemic-induced hiatus in clinical trials in general.

Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.

During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.

Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.

“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.

The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
 

Program to increase underrepresented patient accrual

The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.

“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.

“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
 

What works?

The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”

“I’m going to violate the rules of your question,” Dr. Paskett replied.

“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.

She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.

Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:

• Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
• Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
• Translation of informational materials for patients.
• Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
• Real-time monitoring of accrual demographics by the Alliance and at the trial site.
• Closing protocol enrollment to majority populations.
• Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.

The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.

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

CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.

Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.

A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.

In the randomized controlled RESTORE study, use of the cell phone–based CBSM app was associated with significantly greater reduction in symptoms of anxiety and depression compared with a digital health education control app.

In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).

However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.

The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.

“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.

“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
 

Impressive and elegant

“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.

“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.

CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.

To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.

Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.

They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
 

High-quality control

Ms. Ramiller said that the control app set “a high bar.”

“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.

A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.

The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).

CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)

An extension study of the durability of the effects at 3 and 6 months is underway.

The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.

“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”

The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
 

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

CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.

Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.

A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.

In the randomized controlled RESTORE study, use of the cell phone–based CBSM app was associated with significantly greater reduction in symptoms of anxiety and depression compared with a digital health education control app.

In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).

However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.

The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.

“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.

“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
 

Impressive and elegant

“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.

“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.

CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.

To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.

Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.

They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
 

High-quality control

Ms. Ramiller said that the control app set “a high bar.”

“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.

A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.

The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).

CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)

An extension study of the durability of the effects at 3 and 6 months is underway.

The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.

“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”

The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
 

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

CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.

Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.

A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.

In the randomized controlled RESTORE study, use of the cell phone–based CBSM app was associated with significantly greater reduction in symptoms of anxiety and depression compared with a digital health education control app.

In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).

However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.

The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.

“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.

“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
 

Impressive and elegant

“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.

“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.

CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.

To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.

Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.

They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
 

High-quality control

Ms. Ramiller said that the control app set “a high bar.”

“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.

A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.

The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).

CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)

An extension study of the durability of the effects at 3 and 6 months is underway.

The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.

“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”

The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
 

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

TOPLINE:

A family history of breast cancer does not necessarily mean that women who have the disease are more likely to die from it.

METHODOLOGY:

• Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
• Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.

TAKEAWAYS:

• After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
• The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
• However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).

IN PRACTICE:

Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.

STUDY DETAILS:

The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.

LIMITATIONS:

• The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
• Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.

DISCLOSURES:

• The work was funded by the Swedish Cancer Society and others.
• The investigators report no relevant financial relationships.

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

TOPLINE:

A family history of breast cancer does not necessarily mean that women who have the disease are more likely to die from it.

METHODOLOGY:

• Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
• Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.

TAKEAWAYS:

• After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
• The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
• However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).

IN PRACTICE:

Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.

STUDY DETAILS:

The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.

LIMITATIONS:

• The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
• Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.

DISCLOSURES:

• The work was funded by the Swedish Cancer Society and others.
• The investigators report no relevant financial relationships.

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

TOPLINE:

A family history of breast cancer does not necessarily mean that women who have the disease are more likely to die from it.

METHODOLOGY:

• Investigators reviewed 28,649 Swedish women diagnosed with breast cancer from 1991 to 2019.
• Overall, 5,081 patients (17.7%) had at least one female first-degree relative previously diagnosed with breast cancer.

TAKEAWAYS:

• After adjusting for demographics, tumor characteristics, and treatments, a family history of breast cancer was associated with a lower risk of breast cancer–specific death in the full cohort (hazard ratio, 0.78) and in ER-negative women (HR, 0.57) within 5 years of diagnosis, after which point the association was no longer significant.
• The lower risk of death among women with a family history could mean that these women are more motivated and likely to get screened, potentially catching tumors earlier, and may be more likely to adhere to treatment recommendations.
• However, having a family history of early-onset breast cancer (before the age of 40) was associated with a higher risk of breast cancer–specific death (HR, 1.41).

IN PRACTICE:

Although the findings are reassuring for many women with breast cancer, “genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research,” the researchers concluded.

STUDY DETAILS:

The study was led by Yuqi Zhang, PhD, of the Karolinska Institutet, Stockholm, and published in JAMA Network Open.

LIMITATIONS:

• The main analysis did not include tumor characteristics only available within the last 20 years, including ERBB2 status.
• Relatively wide confidence intervals make the association between a family history of early-onset breast cancer and higher risk of breast cancer death somewhat uncertain.

DISCLOSURES:

• The work was funded by the Swedish Cancer Society and others.
• The investigators report no relevant financial relationships.

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

CHICAGO – Trastuzumab deruxtecan (T-DXd) (Enhertu) already has proven efficacy against HER2-expressing metastatic breast, gastroesophageal, and lung cancers.

Now, preliminary data from an ongoing study indicate that T-DXd, which combines an antibody targeted to HER2 with a toxic payload, could be an effective therapy for a broader range of advanced solid tumors that express HER2, including malignancies of the cervix, endometrium, ovaries, bladder, and other sites.

The findings come from the ongoing DESTINY-PanTumor02 trial. Among 267 patients with solid tumors at various organ sites, the investigator-assessed objective response rate among all patients was 37.1%, and ranged from as high as 57.5% for patients with endometrial cancers to as low as 4% for patients with pancreatic cancer, reported Funda Meric-Bernstam, MD, from the University of Texas MD Anderson Cancer Center, Houston.

For patients with tumors that had HER2 immunohistochemistry (IHC) scores of 3+, the highest level of HER2 expression, the overall response rate was 61.3%..

The responses were also durable, with a median duration of 11.8 months among all patients and 22.1 months among patients with IHC 3+ scores.

“Our data to date showed that T-DXd had clinically meaningful activity across a variety of tumor types,” she said in a briefing held prior to her presentation of the data at the annual meeting of the American Society of Clinical Oncology.

“HER2 expression has been around a long time. We think about this all the time in breast cancer and drugs are approved there, but HER2 is expressed in other tumors as well, and that really represents an unmet need, because we have limited options in this situation” commented ASCO expert Bradley Alexander McGregor, MD, from the Dana-Farber Cancer Institute, Boston, an invited discussant at the briefing.

“Aside from pancreatic cancer we saw really, really encouraging results with no new safety signals, so while early I think this really exciting and represents a shift in how we think about cancer care,” he added.

After the presentation, invited discussant Kohei Shitara, MD, of National Cancer Center Hospital East, Kashiwa, Japan, said that he agrees with authors that T-DXd is a potential new treatment option for patients with HER2-expressing solid tumors, and that the evidence suggests the potential for further tumor-agnostic development of the agent.

He cautioned, however, that there is a lack of concordance between local and central assessment of HER2 IHC, and that quality assurance will be required to ensure that the HER2 status of solid tumors is accurately characterized.

At a press briefing, Dr. Meric-Bernstam was asked how she envisioned using T-DXd in therapy for various HER2-expressing tumors.

“I think the activity we’ve seen is quite compelling, and one hopes that eventually this will be a drug that’s accessible for patients that are HER2-expressing across tumor types. Clearly, the activity is very compelling in some of the diseases to think about doing studies for earlier lines,” she said.

“The data indicate that there is tumor-agnostic activity across the board,” she said, but noted that tumors with epithelial components such as ovarian and breast cancers appear to have the highest responses to T-DXd therapy.

Briefing moderator Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, asked Dr. McGregor whether, in the light of this new data, oncologists should test more patients for HER2 expression.

“We have some cancers where we know HER2 expression is there. I think the good thing about HER2 testing is that it’s an IHC test, so this is something that can be easily done in local pathology [labs],” he said. As more evidence mounts of potential benefit of T-DXd in HER2 expressing tumors, clinicians will need to consider more routine HER2 testing.
 

A rendezvous with DESTINY

The DESTINY-PanTumor02 trial is a phase 2, open-label, multicenter study looking at T-DXd in patients with advanced solid tumors who are not eligible for therapy with curative intent.

All patients had disease progression after at least two prior lines of therapy, and had tumors with HER2 expression of IHC 3+ or 2+ either by local or central testing. Patients were allowed to have previously received HER2-targeting therapy. Patients also had to have good performance status (Eastern Cooperative Oncology Group/World Health Organization performance status 0 or 1).

The investigators planned to enroll 40 patients in each cohort, including patients with cervical, endometrial, ovarian, biliary tract, pancreatic, or bladder cancers, as well those with other tumors expressing HER2 who were not included in the other cohorts.

Under the protocol, cohorts in which none of the first 15 patients had objective responses would be closed, as happened with the pancreatic cancer cohort.

At a median follow-up of 9.7 months, an objective response was seen in 99 patients out of the 267 in the entire study population (ORR, 37.1%). This ORR consisted of 15 complete responses and 84 partial responses. An additional 123 patients had stable disease.

An analysis of ORR by HER2 expression showed that IHC 3+ expressing tumors had rates ranging from 84.6% in endometrial cancers, 75% in cervical cancer, 63.6% in ovarian cancers, and 56.3% in bladder cancers, down to zero in IHC 3+ expressing pancreatic cancer. 

The T-DXd safety profile was consistent with that seen in other clinical trials, with most common adverse events being nausea, fatigue, neutropenia, anemia, diarrhea, and thrombocytopenia. There were 20 cases of interstitial lung disease, one of which was fatal.

The trial is ongoing, and investigators plan to report overall survival and progression-free survival results with additional follow-up.

DESTINY-PanTumor02 is funded by Daiichi Sankyo. Dr. Meric-Bernstam disclosed a consulting/advisory role with multiple pharmaceutical companies, research funding to her institution from Daiichi Sankyo and others, and travel expenses from ESMO and EORTC. Dr. McGregor disclosed a consulting/advisory role and institutional research funding with multiple companies, not including the study’s funder. Dr. Gralow disclosed a consulting or advisory role with Genentech and Roche.

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

CHICAGO – Trastuzumab deruxtecan (T-DXd) (Enhertu) already has proven efficacy against HER2-expressing metastatic breast, gastroesophageal, and lung cancers.

Now, preliminary data from an ongoing study indicate that T-DXd, which combines an antibody targeted to HER2 with a toxic payload, could be an effective therapy for a broader range of advanced solid tumors that express HER2, including malignancies of the cervix, endometrium, ovaries, bladder, and other sites.

The findings come from the ongoing DESTINY-PanTumor02 trial. Among 267 patients with solid tumors at various organ sites, the investigator-assessed objective response rate among all patients was 37.1%, and ranged from as high as 57.5% for patients with endometrial cancers to as low as 4% for patients with pancreatic cancer, reported Funda Meric-Bernstam, MD, from the University of Texas MD Anderson Cancer Center, Houston.

For patients with tumors that had HER2 immunohistochemistry (IHC) scores of 3+, the highest level of HER2 expression, the overall response rate was 61.3%..

The responses were also durable, with a median duration of 11.8 months among all patients and 22.1 months among patients with IHC 3+ scores.

“Our data to date showed that T-DXd had clinically meaningful activity across a variety of tumor types,” she said in a briefing held prior to her presentation of the data at the annual meeting of the American Society of Clinical Oncology.

“HER2 expression has been around a long time. We think about this all the time in breast cancer and drugs are approved there, but HER2 is expressed in other tumors as well, and that really represents an unmet need, because we have limited options in this situation” commented ASCO expert Bradley Alexander McGregor, MD, from the Dana-Farber Cancer Institute, Boston, an invited discussant at the briefing.

“Aside from pancreatic cancer we saw really, really encouraging results with no new safety signals, so while early I think this really exciting and represents a shift in how we think about cancer care,” he added.

After the presentation, invited discussant Kohei Shitara, MD, of National Cancer Center Hospital East, Kashiwa, Japan, said that he agrees with authors that T-DXd is a potential new treatment option for patients with HER2-expressing solid tumors, and that the evidence suggests the potential for further tumor-agnostic development of the agent.

He cautioned, however, that there is a lack of concordance between local and central assessment of HER2 IHC, and that quality assurance will be required to ensure that the HER2 status of solid tumors is accurately characterized.

At a press briefing, Dr. Meric-Bernstam was asked how she envisioned using T-DXd in therapy for various HER2-expressing tumors.

“I think the activity we’ve seen is quite compelling, and one hopes that eventually this will be a drug that’s accessible for patients that are HER2-expressing across tumor types. Clearly, the activity is very compelling in some of the diseases to think about doing studies for earlier lines,” she said.

“The data indicate that there is tumor-agnostic activity across the board,” she said, but noted that tumors with epithelial components such as ovarian and breast cancers appear to have the highest responses to T-DXd therapy.

Briefing moderator Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, asked Dr. McGregor whether, in the light of this new data, oncologists should test more patients for HER2 expression.

“We have some cancers where we know HER2 expression is there. I think the good thing about HER2 testing is that it’s an IHC test, so this is something that can be easily done in local pathology [labs],” he said. As more evidence mounts of potential benefit of T-DXd in HER2 expressing tumors, clinicians will need to consider more routine HER2 testing.
 

A rendezvous with DESTINY

The DESTINY-PanTumor02 trial is a phase 2, open-label, multicenter study looking at T-DXd in patients with advanced solid tumors who are not eligible for therapy with curative intent.

All patients had disease progression after at least two prior lines of therapy, and had tumors with HER2 expression of IHC 3+ or 2+ either by local or central testing. Patients were allowed to have previously received HER2-targeting therapy. Patients also had to have good performance status (Eastern Cooperative Oncology Group/World Health Organization performance status 0 or 1).

The investigators planned to enroll 40 patients in each cohort, including patients with cervical, endometrial, ovarian, biliary tract, pancreatic, or bladder cancers, as well those with other tumors expressing HER2 who were not included in the other cohorts.

Under the protocol, cohorts in which none of the first 15 patients had objective responses would be closed, as happened with the pancreatic cancer cohort.

At a median follow-up of 9.7 months, an objective response was seen in 99 patients out of the 267 in the entire study population (ORR, 37.1%). This ORR consisted of 15 complete responses and 84 partial responses. An additional 123 patients had stable disease.

An analysis of ORR by HER2 expression showed that IHC 3+ expressing tumors had rates ranging from 84.6% in endometrial cancers, 75% in cervical cancer, 63.6% in ovarian cancers, and 56.3% in bladder cancers, down to zero in IHC 3+ expressing pancreatic cancer. 

The T-DXd safety profile was consistent with that seen in other clinical trials, with most common adverse events being nausea, fatigue, neutropenia, anemia, diarrhea, and thrombocytopenia. There were 20 cases of interstitial lung disease, one of which was fatal.

The trial is ongoing, and investigators plan to report overall survival and progression-free survival results with additional follow-up.

DESTINY-PanTumor02 is funded by Daiichi Sankyo. Dr. Meric-Bernstam disclosed a consulting/advisory role with multiple pharmaceutical companies, research funding to her institution from Daiichi Sankyo and others, and travel expenses from ESMO and EORTC. Dr. McGregor disclosed a consulting/advisory role and institutional research funding with multiple companies, not including the study’s funder. Dr. Gralow disclosed a consulting or advisory role with Genentech and Roche.

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

CHICAGO – Trastuzumab deruxtecan (T-DXd) (Enhertu) already has proven efficacy against HER2-expressing metastatic breast, gastroesophageal, and lung cancers.

Now, preliminary data from an ongoing study indicate that T-DXd, which combines an antibody targeted to HER2 with a toxic payload, could be an effective therapy for a broader range of advanced solid tumors that express HER2, including malignancies of the cervix, endometrium, ovaries, bladder, and other sites.

The findings come from the ongoing DESTINY-PanTumor02 trial. Among 267 patients with solid tumors at various organ sites, the investigator-assessed objective response rate among all patients was 37.1%, and ranged from as high as 57.5% for patients with endometrial cancers to as low as 4% for patients with pancreatic cancer, reported Funda Meric-Bernstam, MD, from the University of Texas MD Anderson Cancer Center, Houston.

For patients with tumors that had HER2 immunohistochemistry (IHC) scores of 3+, the highest level of HER2 expression, the overall response rate was 61.3%..

The responses were also durable, with a median duration of 11.8 months among all patients and 22.1 months among patients with IHC 3+ scores.

“Our data to date showed that T-DXd had clinically meaningful activity across a variety of tumor types,” she said in a briefing held prior to her presentation of the data at the annual meeting of the American Society of Clinical Oncology.

“HER2 expression has been around a long time. We think about this all the time in breast cancer and drugs are approved there, but HER2 is expressed in other tumors as well, and that really represents an unmet need, because we have limited options in this situation” commented ASCO expert Bradley Alexander McGregor, MD, from the Dana-Farber Cancer Institute, Boston, an invited discussant at the briefing.

“Aside from pancreatic cancer we saw really, really encouraging results with no new safety signals, so while early I think this really exciting and represents a shift in how we think about cancer care,” he added.

After the presentation, invited discussant Kohei Shitara, MD, of National Cancer Center Hospital East, Kashiwa, Japan, said that he agrees with authors that T-DXd is a potential new treatment option for patients with HER2-expressing solid tumors, and that the evidence suggests the potential for further tumor-agnostic development of the agent.

He cautioned, however, that there is a lack of concordance between local and central assessment of HER2 IHC, and that quality assurance will be required to ensure that the HER2 status of solid tumors is accurately characterized.

At a press briefing, Dr. Meric-Bernstam was asked how she envisioned using T-DXd in therapy for various HER2-expressing tumors.

“I think the activity we’ve seen is quite compelling, and one hopes that eventually this will be a drug that’s accessible for patients that are HER2-expressing across tumor types. Clearly, the activity is very compelling in some of the diseases to think about doing studies for earlier lines,” she said.

“The data indicate that there is tumor-agnostic activity across the board,” she said, but noted that tumors with epithelial components such as ovarian and breast cancers appear to have the highest responses to T-DXd therapy.

Briefing moderator Julie R. Gralow, MD, chief medical officer and executive vice president of ASCO, asked Dr. McGregor whether, in the light of this new data, oncologists should test more patients for HER2 expression.

“We have some cancers where we know HER2 expression is there. I think the good thing about HER2 testing is that it’s an IHC test, so this is something that can be easily done in local pathology [labs],” he said. As more evidence mounts of potential benefit of T-DXd in HER2 expressing tumors, clinicians will need to consider more routine HER2 testing.
 

A rendezvous with DESTINY

The DESTINY-PanTumor02 trial is a phase 2, open-label, multicenter study looking at T-DXd in patients with advanced solid tumors who are not eligible for therapy with curative intent.

All patients had disease progression after at least two prior lines of therapy, and had tumors with HER2 expression of IHC 3+ or 2+ either by local or central testing. Patients were allowed to have previously received HER2-targeting therapy. Patients also had to have good performance status (Eastern Cooperative Oncology Group/World Health Organization performance status 0 or 1).

The investigators planned to enroll 40 patients in each cohort, including patients with cervical, endometrial, ovarian, biliary tract, pancreatic, or bladder cancers, as well those with other tumors expressing HER2 who were not included in the other cohorts.

Under the protocol, cohorts in which none of the first 15 patients had objective responses would be closed, as happened with the pancreatic cancer cohort.

At a median follow-up of 9.7 months, an objective response was seen in 99 patients out of the 267 in the entire study population (ORR, 37.1%). This ORR consisted of 15 complete responses and 84 partial responses. An additional 123 patients had stable disease.

An analysis of ORR by HER2 expression showed that IHC 3+ expressing tumors had rates ranging from 84.6% in endometrial cancers, 75% in cervical cancer, 63.6% in ovarian cancers, and 56.3% in bladder cancers, down to zero in IHC 3+ expressing pancreatic cancer. 

The T-DXd safety profile was consistent with that seen in other clinical trials, with most common adverse events being nausea, fatigue, neutropenia, anemia, diarrhea, and thrombocytopenia. There were 20 cases of interstitial lung disease, one of which was fatal.

The trial is ongoing, and investigators plan to report overall survival and progression-free survival results with additional follow-up.

DESTINY-PanTumor02 is funded by Daiichi Sankyo. Dr. Meric-Bernstam disclosed a consulting/advisory role with multiple pharmaceutical companies, research funding to her institution from Daiichi Sankyo and others, and travel expenses from ESMO and EORTC. Dr. McGregor disclosed a consulting/advisory role and institutional research funding with multiple companies, not including the study’s funder. Dr. Gralow disclosed a consulting or advisory role with Genentech and Roche.

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

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

Key clinical point: Higher genetic susceptibility to breast cancer (BC) is associated with an increased risk for overall thyroid cancer; however, this association is not valid in case of triple-negative BC (TNBC) and thyroid cancer.

Major finding: The risk for thyroid cancer was significantly elevated in patients with BC (odds ratio 1.135; P = .038); however, no causal link was observed between TNBC and thyroid cancer (OR 0.817; P = .177).

Study details: Findings are from a two-sample mendelian randomization analysis including 133,384 patients with BC and 113,789 BC-free control individuals.

Disclosures: This study was supported by funding from the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Tan H et al. Association between breast cancer and thyroid cancer risk: A two-sample Mendelian randomization study. Front Endocrinol (Lausanne). 2023;14:1138149 (May 23). doi: 10.3389/fendo.2023.1138149

Key clinical point: Higher genetic susceptibility to breast cancer (BC) is associated with an increased risk for overall thyroid cancer; however, this association is not valid in case of triple-negative BC (TNBC) and thyroid cancer.

Major finding: The risk for thyroid cancer was significantly elevated in patients with BC (odds ratio 1.135; P = .038); however, no causal link was observed between TNBC and thyroid cancer (OR 0.817; P = .177).

Study details: Findings are from a two-sample mendelian randomization analysis including 133,384 patients with BC and 113,789 BC-free control individuals.

Disclosures: This study was supported by funding from the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Tan H et al. Association between breast cancer and thyroid cancer risk: A two-sample Mendelian randomization study. Front Endocrinol (Lausanne). 2023;14:1138149 (May 23). doi: 10.3389/fendo.2023.1138149

Key clinical point: Higher genetic susceptibility to breast cancer (BC) is associated with an increased risk for overall thyroid cancer; however, this association is not valid in case of triple-negative BC (TNBC) and thyroid cancer.

Major finding: The risk for thyroid cancer was significantly elevated in patients with BC (odds ratio 1.135; P = .038); however, no causal link was observed between TNBC and thyroid cancer (OR 0.817; P = .177).

Study details: Findings are from a two-sample mendelian randomization analysis including 133,384 patients with BC and 113,789 BC-free control individuals.

Disclosures: This study was supported by funding from the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Tan H et al. Association between breast cancer and thyroid cancer risk: A two-sample Mendelian randomization study. Front Endocrinol (Lausanne). 2023;14:1138149 (May 23). doi: 10.3389/fendo.2023.1138149

Key clinical point: In patients with early-stage breast cancer (BC), breast conserving surgery with radiotherapy (BCT) provided a significant survival advantage over total mastectomy (TM) without increasing the rates of locoregional recurrence.

Major finding: BCT vs TM improved overall survival by 37% (hazard ratio [HR] 1.37; P < .001) and BC-specific survival by 49% (HR 1.49; P < .001), with rates of locoregional recurrence (P > .9) being comparable between the groups.

Study details: This study analyzed the data of 12,456 patients with pT1-2 pN0 BC from a prospectively maintained database, of which 8422 and 4034 patients underwent BCT and TM, respectively.

Disclosures: This study did not report the source of funding. The authors did not report any conflicts of interest.

Source: Vasilyeva E et al. Breast conserving surgery combined with radiation therapy offers improved survival over mastectomy in early-stage breast cancer. Am J Surg. 2023 (May 22). doi: 10.1016/j.amjsurg.2023.05.005

Key clinical point: In patients with early-stage breast cancer (BC), breast conserving surgery with radiotherapy (BCT) provided a significant survival advantage over total mastectomy (TM) without increasing the rates of locoregional recurrence.

Major finding: BCT vs TM improved overall survival by 37% (hazard ratio [HR] 1.37; P < .001) and BC-specific survival by 49% (HR 1.49; P < .001), with rates of locoregional recurrence (P > .9) being comparable between the groups.

Study details: This study analyzed the data of 12,456 patients with pT1-2 pN0 BC from a prospectively maintained database, of which 8422 and 4034 patients underwent BCT and TM, respectively.

Disclosures: This study did not report the source of funding. The authors did not report any conflicts of interest.

Source: Vasilyeva E et al. Breast conserving surgery combined with radiation therapy offers improved survival over mastectomy in early-stage breast cancer. Am J Surg. 2023 (May 22). doi: 10.1016/j.amjsurg.2023.05.005

Key clinical point: In patients with early-stage breast cancer (BC), breast conserving surgery with radiotherapy (BCT) provided a significant survival advantage over total mastectomy (TM) without increasing the rates of locoregional recurrence.

Major finding: BCT vs TM improved overall survival by 37% (hazard ratio [HR] 1.37; P < .001) and BC-specific survival by 49% (HR 1.49; P < .001), with rates of locoregional recurrence (P > .9) being comparable between the groups.

Study details: This study analyzed the data of 12,456 patients with pT1-2 pN0 BC from a prospectively maintained database, of which 8422 and 4034 patients underwent BCT and TM, respectively.

Disclosures: This study did not report the source of funding. The authors did not report any conflicts of interest.

Source: Vasilyeva E et al. Breast conserving surgery combined with radiation therapy offers improved survival over mastectomy in early-stage breast cancer. Am J Surg. 2023 (May 22). doi: 10.1016/j.amjsurg.2023.05.005

Key clinical point: Men with a family history of breast cancer (FHBC) in either mother or sister are at a higher risk of developing pancreatic, thyroid, prostate, and breast cancers than men without FHBC and, therefore, may need more vigilant cancer surveillance.

Major finding: An FHBC in both mother and sister was associated with an increased overall cancer risk (hazard ratio [HR] 1.69; 95% CI 1.11-2.57), whereas an FHBC in either mother or sister significantly increased the risk of developing pancreatic cancer (HR 1.35; 95% CI 1.07-1.70), breast cancer (HR 3.03; 95% CI 1.13-8.17), thyroid cancer (HR 1.33; 95% CI 1.12-1.56), and prostate cancer (HR 1.28; 95% CI 1.13-1.44).

Study details: Findings are from a population-based study including 2,734,889 men aged ≥40 years, of which 69,124 men had a FHBC in their mother or sister and 276,496 men had no history of cancer in any of their first-degree relatives.

Disclosures: This study was supported by a National Research Foundation of Korea grant. The authors declared no conflicts of interest.

Source: Song H, Jung YS, et al. Increased risk of pancreatic, thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study. Int J Cancer. 2023 (May 29). doi: 10.1002/ijc.34573

Key clinical point: Men with a family history of breast cancer (FHBC) in either mother or sister are at a higher risk of developing pancreatic, thyroid, prostate, and breast cancers than men without FHBC and, therefore, may need more vigilant cancer surveillance.

Major finding: An FHBC in both mother and sister was associated with an increased overall cancer risk (hazard ratio [HR] 1.69; 95% CI 1.11-2.57), whereas an FHBC in either mother or sister significantly increased the risk of developing pancreatic cancer (HR 1.35; 95% CI 1.07-1.70), breast cancer (HR 3.03; 95% CI 1.13-8.17), thyroid cancer (HR 1.33; 95% CI 1.12-1.56), and prostate cancer (HR 1.28; 95% CI 1.13-1.44).

Study details: Findings are from a population-based study including 2,734,889 men aged ≥40 years, of which 69,124 men had a FHBC in their mother or sister and 276,496 men had no history of cancer in any of their first-degree relatives.

Disclosures: This study was supported by a National Research Foundation of Korea grant. The authors declared no conflicts of interest.

Source: Song H, Jung YS, et al. Increased risk of pancreatic, thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study. Int J Cancer. 2023 (May 29). doi: 10.1002/ijc.34573

Key clinical point: Men with a family history of breast cancer (FHBC) in either mother or sister are at a higher risk of developing pancreatic, thyroid, prostate, and breast cancers than men without FHBC and, therefore, may need more vigilant cancer surveillance.

Major finding: An FHBC in both mother and sister was associated with an increased overall cancer risk (hazard ratio [HR] 1.69; 95% CI 1.11-2.57), whereas an FHBC in either mother or sister significantly increased the risk of developing pancreatic cancer (HR 1.35; 95% CI 1.07-1.70), breast cancer (HR 3.03; 95% CI 1.13-8.17), thyroid cancer (HR 1.33; 95% CI 1.12-1.56), and prostate cancer (HR 1.28; 95% CI 1.13-1.44).

Study details: Findings are from a population-based study including 2,734,889 men aged ≥40 years, of which 69,124 men had a FHBC in their mother or sister and 276,496 men had no history of cancer in any of their first-degree relatives.

Disclosures: This study was supported by a National Research Foundation of Korea grant. The authors declared no conflicts of interest.

Source: Song H, Jung YS, et al. Increased risk of pancreatic, thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study. Int J Cancer. 2023 (May 29). doi: 10.1002/ijc.34573