AVAHO

The Food and Drug Administration has approved the oral poly (ADP-ribose) polymerase inhibitor talazoparib (Talzenna, Pfizer) plus enzalutamide (Xtandi) to treat homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer.

Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.

The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).

Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.

Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.

“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”

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

The Food and Drug Administration has approved the oral poly (ADP-ribose) polymerase inhibitor talazoparib (Talzenna, Pfizer) plus enzalutamide (Xtandi) to treat homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer.

Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.

The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).

Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.

Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.

“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”

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

The Food and Drug Administration has approved the oral poly (ADP-ribose) polymerase inhibitor talazoparib (Talzenna, Pfizer) plus enzalutamide (Xtandi) to treat homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer.

Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.

The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).

Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.

Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.

“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”

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.

A Massachusetts-based law firm has filed a class action lawsuit against Harvard Medical School, alleging that it failed to protect the remains of people who donated their bodies to the university for research and education.

Plaintiffs include relatives of people whose remains were allegedly stolen and sold. The lawsuit alleges that as many as 400 cadavers may have been trafficked in a multi-year scheme. Details were revealed in a June 13 indictment by the U.S. attorney for the Middle District of Pennsylvania.

“Medical schools like Harvard have a duty to ensure [donated remains] are handled properly and with decency and to ensure they are used for their intended purpose of scientific study,” attorney Jeff Catalano said in a statement.

“I do think Harvard has that duty,” said Arthur Caplan, PhD, director, Division of Medical Ethics, New York University. But, he added, “I will say there’s not much they can do when employees set out to systematically undermine them.”

The indictment alleges that from 2018 through August 2022, Harvard morgue manager Cedric Lodge stole dissected portions of donated cadavers, including heads, brains, skin, and bones, which were then sold by him and his wife, Denise Lodge, to Katrina Maclean, owner of Kat’s Creepy Creations, Peabody, Mass. Ms. Maclean allegedly sold human remains to Joshua Taylor and Jeremy Pauley, both Pennsylvania residents.

On occasion, Mr. Lodge allowed Ms. Maclean, Mr. Taylor, and others into the morgue to choose which parts they wanted, according to the indictment. Mr. Taylor, Ms. Maclean, and Denise Lodge are all named in the indictment. Mr. Pauley was charged separately.

They each face a maximum of 15 years in prison.

Ms. Maclean allegedly bought two dissected faces for $600 and shipped human skin to Mr. Pauley to be made into leather; Mr. Pauley then eventually shipped the “tanned human skin” back to Ms. Maclean, according to the indictment. Over a 3-year period, Mr. Taylor paid the Lodges some $37,000 for stolen human remains, the indictment charges.

Mr. Pauley also purchased human remains from Candace Chapman Scott, who stole them from her employer, a mortuary in Little Rock, Ark. The mortuary received remains for cremation from an area medical school, according to the indictment.

After being notified of the investigation in March, Harvard cooperated fully, the school said in a statement from George Q. Daley, MD, PhD, dean of the Faculty of Medicine.

“We are appalled to learn that something so disturbing could happen on our campus – a community dedicated to healing and serving others,” the statement said. “The reported incidents are a betrayal of HMS and, most importantly, each of the individuals who altruistically chose to will their bodies to HMS through the Anatomical Gift Program to advance medical education and research.”

The U.S. attorney thanked Harvard for its cooperation, saying that it “is also a victim here.”

Dr. Caplan, who also writes an ethics column for this news organization, agrees. The school was betrayed, he said.

“You expect professionalism, integrity on the part of your doctors, on the part of your technicians, on the part of your workforce,” he said. He noted that those expectations are explained in institutions’ codes of ethics and policies.

Harvard said Mr. Lodge had worked in the morgue since 1995 and that he took several leaves: from September 2021 to February 2022, and again starting February 14. The school terminated his employment on May 6.

His duties included intake of anatomic donors’ bodies. He coordinated embalming and oversaw the storage and movement of cadavers to and from teaching labs. When studies were complete, he prepared remains to be transported to and from the external crematorium and, when appropriate, for burial, according to a Harvard fact sheet for families.

The medical school has convened an outside expert panel to evaluate the Anatomical Gift Program and morgue policies and practices. The panel is expected to make its findings public at the end of the summer.

Dr. Caplan said he hoped the committee recommends unannounced audits of cadaver donation programs and medical tissue and bone suppliers, which could help expose illicit diversions. “You need to keep an eye, which no one seems to do because it’s a state issue and it’s not a priority, on that trade in body parts,” he said.

He believes other medical schools will reexamine their donation programs, especially given Harvard’s status.

“With a prominent place like that having this kind of problem, I can’t imagine there’s not a little bit of a scramble at a lot of the body programs to make sure that they know that things are as they should be,” Dr. Caplan said.

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

A Massachusetts-based law firm has filed a class action lawsuit against Harvard Medical School, alleging that it failed to protect the remains of people who donated their bodies to the university for research and education.

Plaintiffs include relatives of people whose remains were allegedly stolen and sold. The lawsuit alleges that as many as 400 cadavers may have been trafficked in a multi-year scheme. Details were revealed in a June 13 indictment by the U.S. attorney for the Middle District of Pennsylvania.

“Medical schools like Harvard have a duty to ensure [donated remains] are handled properly and with decency and to ensure they are used for their intended purpose of scientific study,” attorney Jeff Catalano said in a statement.

“I do think Harvard has that duty,” said Arthur Caplan, PhD, director, Division of Medical Ethics, New York University. But, he added, “I will say there’s not much they can do when employees set out to systematically undermine them.”

The indictment alleges that from 2018 through August 2022, Harvard morgue manager Cedric Lodge stole dissected portions of donated cadavers, including heads, brains, skin, and bones, which were then sold by him and his wife, Denise Lodge, to Katrina Maclean, owner of Kat’s Creepy Creations, Peabody, Mass. Ms. Maclean allegedly sold human remains to Joshua Taylor and Jeremy Pauley, both Pennsylvania residents.

On occasion, Mr. Lodge allowed Ms. Maclean, Mr. Taylor, and others into the morgue to choose which parts they wanted, according to the indictment. Mr. Taylor, Ms. Maclean, and Denise Lodge are all named in the indictment. Mr. Pauley was charged separately.

They each face a maximum of 15 years in prison.

Ms. Maclean allegedly bought two dissected faces for $600 and shipped human skin to Mr. Pauley to be made into leather; Mr. Pauley then eventually shipped the “tanned human skin” back to Ms. Maclean, according to the indictment. Over a 3-year period, Mr. Taylor paid the Lodges some $37,000 for stolen human remains, the indictment charges.

Mr. Pauley also purchased human remains from Candace Chapman Scott, who stole them from her employer, a mortuary in Little Rock, Ark. The mortuary received remains for cremation from an area medical school, according to the indictment.

After being notified of the investigation in March, Harvard cooperated fully, the school said in a statement from George Q. Daley, MD, PhD, dean of the Faculty of Medicine.

“We are appalled to learn that something so disturbing could happen on our campus – a community dedicated to healing and serving others,” the statement said. “The reported incidents are a betrayal of HMS and, most importantly, each of the individuals who altruistically chose to will their bodies to HMS through the Anatomical Gift Program to advance medical education and research.”

The U.S. attorney thanked Harvard for its cooperation, saying that it “is also a victim here.”

Dr. Caplan, who also writes an ethics column for this news organization, agrees. The school was betrayed, he said.

“You expect professionalism, integrity on the part of your doctors, on the part of your technicians, on the part of your workforce,” he said. He noted that those expectations are explained in institutions’ codes of ethics and policies.

Harvard said Mr. Lodge had worked in the morgue since 1995 and that he took several leaves: from September 2021 to February 2022, and again starting February 14. The school terminated his employment on May 6.

His duties included intake of anatomic donors’ bodies. He coordinated embalming and oversaw the storage and movement of cadavers to and from teaching labs. When studies were complete, he prepared remains to be transported to and from the external crematorium and, when appropriate, for burial, according to a Harvard fact sheet for families.

The medical school has convened an outside expert panel to evaluate the Anatomical Gift Program and morgue policies and practices. The panel is expected to make its findings public at the end of the summer.

Dr. Caplan said he hoped the committee recommends unannounced audits of cadaver donation programs and medical tissue and bone suppliers, which could help expose illicit diversions. “You need to keep an eye, which no one seems to do because it’s a state issue and it’s not a priority, on that trade in body parts,” he said.

He believes other medical schools will reexamine their donation programs, especially given Harvard’s status.

“With a prominent place like that having this kind of problem, I can’t imagine there’s not a little bit of a scramble at a lot of the body programs to make sure that they know that things are as they should be,” Dr. Caplan said.

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

A Massachusetts-based law firm has filed a class action lawsuit against Harvard Medical School, alleging that it failed to protect the remains of people who donated their bodies to the university for research and education.

Plaintiffs include relatives of people whose remains were allegedly stolen and sold. The lawsuit alleges that as many as 400 cadavers may have been trafficked in a multi-year scheme. Details were revealed in a June 13 indictment by the U.S. attorney for the Middle District of Pennsylvania.

“Medical schools like Harvard have a duty to ensure [donated remains] are handled properly and with decency and to ensure they are used for their intended purpose of scientific study,” attorney Jeff Catalano said in a statement.

“I do think Harvard has that duty,” said Arthur Caplan, PhD, director, Division of Medical Ethics, New York University. But, he added, “I will say there’s not much they can do when employees set out to systematically undermine them.”

The indictment alleges that from 2018 through August 2022, Harvard morgue manager Cedric Lodge stole dissected portions of donated cadavers, including heads, brains, skin, and bones, which were then sold by him and his wife, Denise Lodge, to Katrina Maclean, owner of Kat’s Creepy Creations, Peabody, Mass. Ms. Maclean allegedly sold human remains to Joshua Taylor and Jeremy Pauley, both Pennsylvania residents.

On occasion, Mr. Lodge allowed Ms. Maclean, Mr. Taylor, and others into the morgue to choose which parts they wanted, according to the indictment. Mr. Taylor, Ms. Maclean, and Denise Lodge are all named in the indictment. Mr. Pauley was charged separately.

They each face a maximum of 15 years in prison.

Ms. Maclean allegedly bought two dissected faces for $600 and shipped human skin to Mr. Pauley to be made into leather; Mr. Pauley then eventually shipped the “tanned human skin” back to Ms. Maclean, according to the indictment. Over a 3-year period, Mr. Taylor paid the Lodges some $37,000 for stolen human remains, the indictment charges.

Mr. Pauley also purchased human remains from Candace Chapman Scott, who stole them from her employer, a mortuary in Little Rock, Ark. The mortuary received remains for cremation from an area medical school, according to the indictment.

After being notified of the investigation in March, Harvard cooperated fully, the school said in a statement from George Q. Daley, MD, PhD, dean of the Faculty of Medicine.

“We are appalled to learn that something so disturbing could happen on our campus – a community dedicated to healing and serving others,” the statement said. “The reported incidents are a betrayal of HMS and, most importantly, each of the individuals who altruistically chose to will their bodies to HMS through the Anatomical Gift Program to advance medical education and research.”

The U.S. attorney thanked Harvard for its cooperation, saying that it “is also a victim here.”

Dr. Caplan, who also writes an ethics column for this news organization, agrees. The school was betrayed, he said.

“You expect professionalism, integrity on the part of your doctors, on the part of your technicians, on the part of your workforce,” he said. He noted that those expectations are explained in institutions’ codes of ethics and policies.

Harvard said Mr. Lodge had worked in the morgue since 1995 and that he took several leaves: from September 2021 to February 2022, and again starting February 14. The school terminated his employment on May 6.

His duties included intake of anatomic donors’ bodies. He coordinated embalming and oversaw the storage and movement of cadavers to and from teaching labs. When studies were complete, he prepared remains to be transported to and from the external crematorium and, when appropriate, for burial, according to a Harvard fact sheet for families.

The medical school has convened an outside expert panel to evaluate the Anatomical Gift Program and morgue policies and practices. The panel is expected to make its findings public at the end of the summer.

Dr. Caplan said he hoped the committee recommends unannounced audits of cadaver donation programs and medical tissue and bone suppliers, which could help expose illicit diversions. “You need to keep an eye, which no one seems to do because it’s a state issue and it’s not a priority, on that trade in body parts,” he said.

He believes other medical schools will reexamine their donation programs, especially given Harvard’s status.

“With a prominent place like that having this kind of problem, I can’t imagine there’s not a little bit of a scramble at a lot of the body programs to make sure that they know that things are as they should be,” Dr. Caplan said.

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

CHICAGO – Lenalidomide (Revlimid) is a vital component of early therapy and maintenance for patients with multiple myeloma, but patients in first relapse who have disease that is refractory to lenalidomide have few good options for subsequent lines of therapy and a generally poor prognosis.

New results show that such patients benefit from treatment with the chimeric antigen receptor T-cell (CAR T) construct ciltacabtagene autoleucel (cilta-cel) (Carvykti).

The finding comes from the phase 3 CARTITUDE-4 trial, which was reported at the annual meeting of the American Society of Clinical Oncology (ASCO) and was simultaneously published online in the New England Journal of Medicine.

Patients with lenalidomide-refractory multiple myeloma who received a single infusion of ciltacabtagene autoleucel demonstrated a 74% reduction in the risk for disease progression or death, compared with patients who received the standard of care.

The hazard ratio for death or progression with cilta-cel was 0.26 (P < .001), which “is the best hazard ratio ever reported in this patient population in a randomized clinical setting,” said principal investigator Binod Dhakal, MD, from the Medical College of Wisconsin, Milwaukee.

Dr. Dhakal reported data from the first analysis of the trial. At a median follow-up of 15.9 months, median progression-free survival (PFS), the primary endpoint, had not been reached among 208 patients who received cilta-cel; PFS was 11.8 months for the 211 patients assigned to receive standard of care, which consisted of the physician’s choice of either pomalidomide, bortezomib, and dexamethasone (PVd), or daratumumab, pomalidomide, and dexamethasone (DPd).

Twelve-month PFS rates were 75.9% and 48.6%, respectively, and both the overall response rate (ORR) and the complete response (CR) rate were higher with the CAR T construct than with the standard of care (ORR, 84.6% vs. 67.3%; CR rates, 73.1% and 21.8%, respectively).

“My perspective on Dr. Dakhal and colleague’s data is that myeloma treatment should be revisited in the light of this,” commented invited discussant Asher Chanan-Khan, MD, from the Mayo Clinic Cancer Center in Jacksonville, Fla.

“Early CAR Ts demonstrating efficacy and safety and prior lines of treatment impact survival from CAR T in myeloma. In lymphoma, CAR T is almost replacing, if not already, autotransplant. Can this also be true for multiple myeloma?” he asked.

Dr. Chanan-Khan noted that there are at least four ongoing trials with CAR T targeting either the B-cell maturation antigen (BCMA) alone or in combination with an anti-CD19 CAR T, immune checkpoint inhibitors, or with bortezomib, lenalidomide, and dexamethasone.

Also commenting on the new results, ASCO Expert Oreofe Odejide, MD, of the Dana-Farber Cancer Institute in Boston, said in a statement: “Lenalidomide has become a foundation of care for people with myeloma, but as its use has expanded, so has the number of patients whose disease will no longer respond to the treatment. Ciltacabtagene autoleucel has not only shown that it delivers remarkably effective outcomes, compared with patients’ current options, but also that it can be used safely earlier in the treatment phase.”
 

Already approved for refractory myeloma

Cilta-cel is a second-generation CAR T that contains two single-domain antibodies that target BCMA. This target was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells.

The product is already approved for use in myeloma; it was approved in March 2022 by the U.S. Food and Drug Administration for use in patients with refractory/relapsed multiple myeloma who have already tried four or more therapies. That approval was based on results from phase 1b/2 CARTITUDE-1 trial, which, as previously reported by this news organization, showed that early and deep responses with cilta-cel proved to be durable.

Final results of CARTITUDE-1, reported in a scientific poster at ASCO 2023, showed that almost half of patients (47.5%) who were treated with cilta-cel were free of disease progression at 3 years, and 59.8% had sustained, complete responses. In addition, the median PFS was longer than for any previously reported therapy for heavily pretreated patients with relapsed/refractory multiple myeloma, the authors said.
 

CARTITUDE-4 details

For the CARTITUDE-4 trial, the investigators enrolled patients aged 18 years or older with lenalidomide-refractory multiple myeloma who had experienced relapse after one to three prior lines of therapy that included a prosteasome inhibitor and immunomodulator. After stratification by the choice of PVd or DPd, Multiple Myeloma International Staging System, and number of prior lines of therapy, patients were randomly assigned to receive either cilta-cel or one of the two standard-of-care regimens previously described.

Patients assigned to cilta-cel received one or more cycles of either PVd or DPd as bridging therapy during the period from apheresis to infusion of the CAR T cells.

As already noted, cilta-cel showed superior PFS and response rates and was associated with a significantly higher rate of minimal residual disease (MRD) negativity, compared with standard of care, in the intention-to-treat population: 60.6% vs. 15.6%, which translates into an odds ratio for achieving MRD negativity with CAR T of 8.7 (P < .0001). Among the subset of patients evaluable for MRD, the respective rates were 87.5% and 32.7%.

Overall survival data were not mature at the time of presentation. In all, 39 patients in the cilta-cel arm and 47 in the standard-of-care arm died during the study.

Grade 3 or 4 adverse events occurred in 97% of patients who received cilta-cel and in 94% of those who received standard-of-care therapies. In the cilta-cel arm, 76.1% of patients had cytokine release syndrome (CRS), although only 1.1% of cases were of grade 3 or 4 in severity, and there were no CRS-associated deaths. Eight patients in this arm had immune effector cell–associated neurotoxicity syndrome, all of grade 1 or 2. One patient had grade 1 movement and neurocognitive symptoms, 16 had grade 2 or 3 cranial nerve palsy, and 5 patients had CAR T–related peripheral neuropathy of grade 1, 2, or 3.

The investigators plan to follow patients to determine the long-term effects of ciltacabtagene autoleucel and are currently performing analyses of health-related quality of life, subgroups, and biomarkers.

The study was funded by Janssen and Legend Biotech, which market ciltacabtagene autoleucel. Dr. Dhakal disclosed consulting, speaker’s bureau participation, and institutional research funding from Janssen and others. Several coauthors are employees of the study funders. Dr. Chanan-Khan’s relevant financial information was not available. Dr. Odejide reported no relevant financial relationships.

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

CHICAGO – Lenalidomide (Revlimid) is a vital component of early therapy and maintenance for patients with multiple myeloma, but patients in first relapse who have disease that is refractory to lenalidomide have few good options for subsequent lines of therapy and a generally poor prognosis.

New results show that such patients benefit from treatment with the chimeric antigen receptor T-cell (CAR T) construct ciltacabtagene autoleucel (cilta-cel) (Carvykti).

The finding comes from the phase 3 CARTITUDE-4 trial, which was reported at the annual meeting of the American Society of Clinical Oncology (ASCO) and was simultaneously published online in the New England Journal of Medicine.

Patients with lenalidomide-refractory multiple myeloma who received a single infusion of ciltacabtagene autoleucel demonstrated a 74% reduction in the risk for disease progression or death, compared with patients who received the standard of care.

The hazard ratio for death or progression with cilta-cel was 0.26 (P < .001), which “is the best hazard ratio ever reported in this patient population in a randomized clinical setting,” said principal investigator Binod Dhakal, MD, from the Medical College of Wisconsin, Milwaukee.

Dr. Dhakal reported data from the first analysis of the trial. At a median follow-up of 15.9 months, median progression-free survival (PFS), the primary endpoint, had not been reached among 208 patients who received cilta-cel; PFS was 11.8 months for the 211 patients assigned to receive standard of care, which consisted of the physician’s choice of either pomalidomide, bortezomib, and dexamethasone (PVd), or daratumumab, pomalidomide, and dexamethasone (DPd).

Twelve-month PFS rates were 75.9% and 48.6%, respectively, and both the overall response rate (ORR) and the complete response (CR) rate were higher with the CAR T construct than with the standard of care (ORR, 84.6% vs. 67.3%; CR rates, 73.1% and 21.8%, respectively).

“My perspective on Dr. Dakhal and colleague’s data is that myeloma treatment should be revisited in the light of this,” commented invited discussant Asher Chanan-Khan, MD, from the Mayo Clinic Cancer Center in Jacksonville, Fla.

“Early CAR Ts demonstrating efficacy and safety and prior lines of treatment impact survival from CAR T in myeloma. In lymphoma, CAR T is almost replacing, if not already, autotransplant. Can this also be true for multiple myeloma?” he asked.

Dr. Chanan-Khan noted that there are at least four ongoing trials with CAR T targeting either the B-cell maturation antigen (BCMA) alone or in combination with an anti-CD19 CAR T, immune checkpoint inhibitors, or with bortezomib, lenalidomide, and dexamethasone.

Also commenting on the new results, ASCO Expert Oreofe Odejide, MD, of the Dana-Farber Cancer Institute in Boston, said in a statement: “Lenalidomide has become a foundation of care for people with myeloma, but as its use has expanded, so has the number of patients whose disease will no longer respond to the treatment. Ciltacabtagene autoleucel has not only shown that it delivers remarkably effective outcomes, compared with patients’ current options, but also that it can be used safely earlier in the treatment phase.”
 

Already approved for refractory myeloma

Cilta-cel is a second-generation CAR T that contains two single-domain antibodies that target BCMA. This target was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells.

The product is already approved for use in myeloma; it was approved in March 2022 by the U.S. Food and Drug Administration for use in patients with refractory/relapsed multiple myeloma who have already tried four or more therapies. That approval was based on results from phase 1b/2 CARTITUDE-1 trial, which, as previously reported by this news organization, showed that early and deep responses with cilta-cel proved to be durable.

Final results of CARTITUDE-1, reported in a scientific poster at ASCO 2023, showed that almost half of patients (47.5%) who were treated with cilta-cel were free of disease progression at 3 years, and 59.8% had sustained, complete responses. In addition, the median PFS was longer than for any previously reported therapy for heavily pretreated patients with relapsed/refractory multiple myeloma, the authors said.
 

CARTITUDE-4 details

For the CARTITUDE-4 trial, the investigators enrolled patients aged 18 years or older with lenalidomide-refractory multiple myeloma who had experienced relapse after one to three prior lines of therapy that included a prosteasome inhibitor and immunomodulator. After stratification by the choice of PVd or DPd, Multiple Myeloma International Staging System, and number of prior lines of therapy, patients were randomly assigned to receive either cilta-cel or one of the two standard-of-care regimens previously described.

Patients assigned to cilta-cel received one or more cycles of either PVd or DPd as bridging therapy during the period from apheresis to infusion of the CAR T cells.

As already noted, cilta-cel showed superior PFS and response rates and was associated with a significantly higher rate of minimal residual disease (MRD) negativity, compared with standard of care, in the intention-to-treat population: 60.6% vs. 15.6%, which translates into an odds ratio for achieving MRD negativity with CAR T of 8.7 (P < .0001). Among the subset of patients evaluable for MRD, the respective rates were 87.5% and 32.7%.

Overall survival data were not mature at the time of presentation. In all, 39 patients in the cilta-cel arm and 47 in the standard-of-care arm died during the study.

Grade 3 or 4 adverse events occurred in 97% of patients who received cilta-cel and in 94% of those who received standard-of-care therapies. In the cilta-cel arm, 76.1% of patients had cytokine release syndrome (CRS), although only 1.1% of cases were of grade 3 or 4 in severity, and there were no CRS-associated deaths. Eight patients in this arm had immune effector cell–associated neurotoxicity syndrome, all of grade 1 or 2. One patient had grade 1 movement and neurocognitive symptoms, 16 had grade 2 or 3 cranial nerve palsy, and 5 patients had CAR T–related peripheral neuropathy of grade 1, 2, or 3.

The investigators plan to follow patients to determine the long-term effects of ciltacabtagene autoleucel and are currently performing analyses of health-related quality of life, subgroups, and biomarkers.

The study was funded by Janssen and Legend Biotech, which market ciltacabtagene autoleucel. Dr. Dhakal disclosed consulting, speaker’s bureau participation, and institutional research funding from Janssen and others. Several coauthors are employees of the study funders. Dr. Chanan-Khan’s relevant financial information was not available. Dr. Odejide reported no relevant financial relationships.

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

CHICAGO – Lenalidomide (Revlimid) is a vital component of early therapy and maintenance for patients with multiple myeloma, but patients in first relapse who have disease that is refractory to lenalidomide have few good options for subsequent lines of therapy and a generally poor prognosis.

New results show that such patients benefit from treatment with the chimeric antigen receptor T-cell (CAR T) construct ciltacabtagene autoleucel (cilta-cel) (Carvykti).

The finding comes from the phase 3 CARTITUDE-4 trial, which was reported at the annual meeting of the American Society of Clinical Oncology (ASCO) and was simultaneously published online in the New England Journal of Medicine.

Patients with lenalidomide-refractory multiple myeloma who received a single infusion of ciltacabtagene autoleucel demonstrated a 74% reduction in the risk for disease progression or death, compared with patients who received the standard of care.

The hazard ratio for death or progression with cilta-cel was 0.26 (P < .001), which “is the best hazard ratio ever reported in this patient population in a randomized clinical setting,” said principal investigator Binod Dhakal, MD, from the Medical College of Wisconsin, Milwaukee.

Dr. Dhakal reported data from the first analysis of the trial. At a median follow-up of 15.9 months, median progression-free survival (PFS), the primary endpoint, had not been reached among 208 patients who received cilta-cel; PFS was 11.8 months for the 211 patients assigned to receive standard of care, which consisted of the physician’s choice of either pomalidomide, bortezomib, and dexamethasone (PVd), or daratumumab, pomalidomide, and dexamethasone (DPd).

Twelve-month PFS rates were 75.9% and 48.6%, respectively, and both the overall response rate (ORR) and the complete response (CR) rate were higher with the CAR T construct than with the standard of care (ORR, 84.6% vs. 67.3%; CR rates, 73.1% and 21.8%, respectively).

“My perspective on Dr. Dakhal and colleague’s data is that myeloma treatment should be revisited in the light of this,” commented invited discussant Asher Chanan-Khan, MD, from the Mayo Clinic Cancer Center in Jacksonville, Fla.

“Early CAR Ts demonstrating efficacy and safety and prior lines of treatment impact survival from CAR T in myeloma. In lymphoma, CAR T is almost replacing, if not already, autotransplant. Can this also be true for multiple myeloma?” he asked.

Dr. Chanan-Khan noted that there are at least four ongoing trials with CAR T targeting either the B-cell maturation antigen (BCMA) alone or in combination with an anti-CD19 CAR T, immune checkpoint inhibitors, or with bortezomib, lenalidomide, and dexamethasone.

Also commenting on the new results, ASCO Expert Oreofe Odejide, MD, of the Dana-Farber Cancer Institute in Boston, said in a statement: “Lenalidomide has become a foundation of care for people with myeloma, but as its use has expanded, so has the number of patients whose disease will no longer respond to the treatment. Ciltacabtagene autoleucel has not only shown that it delivers remarkably effective outcomes, compared with patients’ current options, but also that it can be used safely earlier in the treatment phase.”
 

Already approved for refractory myeloma

Cilta-cel is a second-generation CAR T that contains two single-domain antibodies that target BCMA. This target was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells.

The product is already approved for use in myeloma; it was approved in March 2022 by the U.S. Food and Drug Administration for use in patients with refractory/relapsed multiple myeloma who have already tried four or more therapies. That approval was based on results from phase 1b/2 CARTITUDE-1 trial, which, as previously reported by this news organization, showed that early and deep responses with cilta-cel proved to be durable.

Final results of CARTITUDE-1, reported in a scientific poster at ASCO 2023, showed that almost half of patients (47.5%) who were treated with cilta-cel were free of disease progression at 3 years, and 59.8% had sustained, complete responses. In addition, the median PFS was longer than for any previously reported therapy for heavily pretreated patients with relapsed/refractory multiple myeloma, the authors said.
 

CARTITUDE-4 details

For the CARTITUDE-4 trial, the investigators enrolled patients aged 18 years or older with lenalidomide-refractory multiple myeloma who had experienced relapse after one to three prior lines of therapy that included a prosteasome inhibitor and immunomodulator. After stratification by the choice of PVd or DPd, Multiple Myeloma International Staging System, and number of prior lines of therapy, patients were randomly assigned to receive either cilta-cel or one of the two standard-of-care regimens previously described.

Patients assigned to cilta-cel received one or more cycles of either PVd or DPd as bridging therapy during the period from apheresis to infusion of the CAR T cells.

As already noted, cilta-cel showed superior PFS and response rates and was associated with a significantly higher rate of minimal residual disease (MRD) negativity, compared with standard of care, in the intention-to-treat population: 60.6% vs. 15.6%, which translates into an odds ratio for achieving MRD negativity with CAR T of 8.7 (P < .0001). Among the subset of patients evaluable for MRD, the respective rates were 87.5% and 32.7%.

Overall survival data were not mature at the time of presentation. In all, 39 patients in the cilta-cel arm and 47 in the standard-of-care arm died during the study.

Grade 3 or 4 adverse events occurred in 97% of patients who received cilta-cel and in 94% of those who received standard-of-care therapies. In the cilta-cel arm, 76.1% of patients had cytokine release syndrome (CRS), although only 1.1% of cases were of grade 3 or 4 in severity, and there were no CRS-associated deaths. Eight patients in this arm had immune effector cell–associated neurotoxicity syndrome, all of grade 1 or 2. One patient had grade 1 movement and neurocognitive symptoms, 16 had grade 2 or 3 cranial nerve palsy, and 5 patients had CAR T–related peripheral neuropathy of grade 1, 2, or 3.

The investigators plan to follow patients to determine the long-term effects of ciltacabtagene autoleucel and are currently performing analyses of health-related quality of life, subgroups, and biomarkers.

The study was funded by Janssen and Legend Biotech, which market ciltacabtagene autoleucel. Dr. Dhakal disclosed consulting, speaker’s bureau participation, and institutional research funding from Janssen and others. Several coauthors are employees of the study funders. Dr. Chanan-Khan’s relevant financial information was not available. Dr. Odejide reported no relevant financial relationships.

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

Omitting race and ethnicity from colorectal cancer (CRC) recurrence risk prediction models could decrease their accuracy and fairness, particularly for minority groups, potentially leading to inappropriate care advice and contributing to existing health disparities, new research suggests.

“Our study has important implications for developing clinical algorithms that are both accurate and fair,” write first author Sara Khor, MASc, with University of Washington, Seattle, and colleagues.

“Many groups have called for the removal of race in clinical algorithms,” Dr. Khor said in an interview. “We wanted to better understand, using CRC recurrence as a case study, what some of the implications might be if we simply remove race as a predictor in a risk prediction algorithm.”

Their findings suggest that doing so could lead to higher racial bias in model accuracy and less accurate estimation of risk for racial and ethnic minority groups. This could lead to inadequate or inappropriate surveillance and follow-up care more often in patients of minoritized racial and ethnic groups.

The study was published online in JAMA Network Open.
 

Lack of data and consensus

There is currently a lack of consensus on whether and how race and ethnicity should be included in clinical risk prediction models used to guide health care decisions, the authors note.

The inclusion of race and ethnicity in clinical risk prediction algorithms has come under increased scrutiny, because of concerns over the potential for racial profiling and biased treatment. On the other hand, some argue that excluding race and ethnicity could harm all groups by reducing predictive accuracy and would especially disadvantage minority groups.

It remains unclear whether simply omitting race and ethnicity from algorithms will ultimately improve care decisions for patients of minoritized racial and ethnic groups.

Dr. Khor and colleagues investigated the performance of four risk prediction models for CRC recurrence using data from 4,230 patients with CRC (53% non-Hispanic white; 22% Hispanic; 13% Black or African American; and 12% Asian, Hawaiian, or Pacific Islander).

The four models were:

• A race-neutral model that explicitly excluded race and ethnicity as a predictor.
• A race-sensitive model that included race and ethnicity.
• A model with two-way interactions between clinical predictors and race and ethnicity.
• Separate models stratified by race and ethnicity.

They found that the race-neutral model had poorer performance (worse calibration, negative predictive value, and false-negative rates) among racial and ethnic minority subgroups, compared with the non-Hispanic subgroup. The false-negative rate for Hispanic patients was 12% vs. 3% for non-Hispanic white patients.

Conversely, including race and ethnicity as a predictor of postoperative cancer recurrence improved the model’s accuracy and increased “algorithmic fairness” in terms of calibration slope, discriminative ability, positive predictive value, and false-negative rates. The false-negative rate for Hispanic patients was 9% and 8% for non-Hispanic white patients.

The inclusion of race interaction terms or using race-stratified models did not improve model fairness, likely due to small sample sizes in subgroups, the authors add.
 

‘No one-size-fits-all answer’

“There is no one-size-fits-all answer to whether race/ethnicity should be included, because the health disparity consequences that can result from each clinical decision are different,” Dr. Khor told this news organization.

“The downstream harms and benefits of including or excluding race will need to be carefully considered in each case,” Dr. Khor said.

“When developing a clinical risk prediction algorithm, one should consider the potential racial/ethnic biases present in clinical practice, which translate to bias in the data,” Dr. Khor added. “Care must be taken to think through the implications of such biases during the algorithm development and evaluation process in order to avoid further propagating those biases.”

The coauthors of a linked commentary say this study “highlights current challenges in measuring and addressing algorithmic bias, with implications for both patient care and health policy decision-making.”

Ankur Pandya, PhD, with Harvard School of Public Health, Boston, and Jinyi Zhu, PhD, with Vanderbilt University, Nashville, Tenn., agree that there is no “one-size-fits-all solution” – such as always excluding race and ethnicity from risk models – to confronting algorithmic bias.

“When possible, approaches for identifying and responding to algorithmic bias should focus on the decisions made by patients and policymakers as they relate to the ultimate outcomes of interest (such as length of life, quality of life, and costs) and the distribution of these outcomes across the subgroups that define important health disparities,” Dr. Pandya and Dr. Zhu suggest.

“What is most promising,” they write, is the high level of engagement from researchers, philosophers, policymakers, physicians and other healthcare professionals, caregivers, and patients to this cause in recent years, “suggesting that algorithmic bias will not be left unchecked as access to unprecedented amounts of data and methods continues to increase moving forward.”

This research was supported by a grant from the National Cancer Institute of the National Institutes of Health. The authors and editorial writers have disclosed no relevant financial relationships.

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

Omitting race and ethnicity from colorectal cancer (CRC) recurrence risk prediction models could decrease their accuracy and fairness, particularly for minority groups, potentially leading to inappropriate care advice and contributing to existing health disparities, new research suggests.

“Our study has important implications for developing clinical algorithms that are both accurate and fair,” write first author Sara Khor, MASc, with University of Washington, Seattle, and colleagues.

“Many groups have called for the removal of race in clinical algorithms,” Dr. Khor said in an interview. “We wanted to better understand, using CRC recurrence as a case study, what some of the implications might be if we simply remove race as a predictor in a risk prediction algorithm.”

Their findings suggest that doing so could lead to higher racial bias in model accuracy and less accurate estimation of risk for racial and ethnic minority groups. This could lead to inadequate or inappropriate surveillance and follow-up care more often in patients of minoritized racial and ethnic groups.

The study was published online in JAMA Network Open.
 

Lack of data and consensus

There is currently a lack of consensus on whether and how race and ethnicity should be included in clinical risk prediction models used to guide health care decisions, the authors note.

The inclusion of race and ethnicity in clinical risk prediction algorithms has come under increased scrutiny, because of concerns over the potential for racial profiling and biased treatment. On the other hand, some argue that excluding race and ethnicity could harm all groups by reducing predictive accuracy and would especially disadvantage minority groups.

It remains unclear whether simply omitting race and ethnicity from algorithms will ultimately improve care decisions for patients of minoritized racial and ethnic groups.

Dr. Khor and colleagues investigated the performance of four risk prediction models for CRC recurrence using data from 4,230 patients with CRC (53% non-Hispanic white; 22% Hispanic; 13% Black or African American; and 12% Asian, Hawaiian, or Pacific Islander).

The four models were:

• A race-neutral model that explicitly excluded race and ethnicity as a predictor.
• A race-sensitive model that included race and ethnicity.
• A model with two-way interactions between clinical predictors and race and ethnicity.
• Separate models stratified by race and ethnicity.

They found that the race-neutral model had poorer performance (worse calibration, negative predictive value, and false-negative rates) among racial and ethnic minority subgroups, compared with the non-Hispanic subgroup. The false-negative rate for Hispanic patients was 12% vs. 3% for non-Hispanic white patients.

Conversely, including race and ethnicity as a predictor of postoperative cancer recurrence improved the model’s accuracy and increased “algorithmic fairness” in terms of calibration slope, discriminative ability, positive predictive value, and false-negative rates. The false-negative rate for Hispanic patients was 9% and 8% for non-Hispanic white patients.

The inclusion of race interaction terms or using race-stratified models did not improve model fairness, likely due to small sample sizes in subgroups, the authors add.
 

‘No one-size-fits-all answer’

“There is no one-size-fits-all answer to whether race/ethnicity should be included, because the health disparity consequences that can result from each clinical decision are different,” Dr. Khor told this news organization.

“The downstream harms and benefits of including or excluding race will need to be carefully considered in each case,” Dr. Khor said.

“When developing a clinical risk prediction algorithm, one should consider the potential racial/ethnic biases present in clinical practice, which translate to bias in the data,” Dr. Khor added. “Care must be taken to think through the implications of such biases during the algorithm development and evaluation process in order to avoid further propagating those biases.”

The coauthors of a linked commentary say this study “highlights current challenges in measuring and addressing algorithmic bias, with implications for both patient care and health policy decision-making.”

Ankur Pandya, PhD, with Harvard School of Public Health, Boston, and Jinyi Zhu, PhD, with Vanderbilt University, Nashville, Tenn., agree that there is no “one-size-fits-all solution” – such as always excluding race and ethnicity from risk models – to confronting algorithmic bias.

“When possible, approaches for identifying and responding to algorithmic bias should focus on the decisions made by patients and policymakers as they relate to the ultimate outcomes of interest (such as length of life, quality of life, and costs) and the distribution of these outcomes across the subgroups that define important health disparities,” Dr. Pandya and Dr. Zhu suggest.

“What is most promising,” they write, is the high level of engagement from researchers, philosophers, policymakers, physicians and other healthcare professionals, caregivers, and patients to this cause in recent years, “suggesting that algorithmic bias will not be left unchecked as access to unprecedented amounts of data and methods continues to increase moving forward.”

This research was supported by a grant from the National Cancer Institute of the National Institutes of Health. The authors and editorial writers have disclosed no relevant financial relationships.

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

Omitting race and ethnicity from colorectal cancer (CRC) recurrence risk prediction models could decrease their accuracy and fairness, particularly for minority groups, potentially leading to inappropriate care advice and contributing to existing health disparities, new research suggests.

“Our study has important implications for developing clinical algorithms that are both accurate and fair,” write first author Sara Khor, MASc, with University of Washington, Seattle, and colleagues.

“Many groups have called for the removal of race in clinical algorithms,” Dr. Khor said in an interview. “We wanted to better understand, using CRC recurrence as a case study, what some of the implications might be if we simply remove race as a predictor in a risk prediction algorithm.”

Their findings suggest that doing so could lead to higher racial bias in model accuracy and less accurate estimation of risk for racial and ethnic minority groups. This could lead to inadequate or inappropriate surveillance and follow-up care more often in patients of minoritized racial and ethnic groups.

The study was published online in JAMA Network Open.
 

Lack of data and consensus

There is currently a lack of consensus on whether and how race and ethnicity should be included in clinical risk prediction models used to guide health care decisions, the authors note.

The inclusion of race and ethnicity in clinical risk prediction algorithms has come under increased scrutiny, because of concerns over the potential for racial profiling and biased treatment. On the other hand, some argue that excluding race and ethnicity could harm all groups by reducing predictive accuracy and would especially disadvantage minority groups.

It remains unclear whether simply omitting race and ethnicity from algorithms will ultimately improve care decisions for patients of minoritized racial and ethnic groups.

Dr. Khor and colleagues investigated the performance of four risk prediction models for CRC recurrence using data from 4,230 patients with CRC (53% non-Hispanic white; 22% Hispanic; 13% Black or African American; and 12% Asian, Hawaiian, or Pacific Islander).

The four models were:

• A race-neutral model that explicitly excluded race and ethnicity as a predictor.
• A race-sensitive model that included race and ethnicity.
• A model with two-way interactions between clinical predictors and race and ethnicity.
• Separate models stratified by race and ethnicity.

They found that the race-neutral model had poorer performance (worse calibration, negative predictive value, and false-negative rates) among racial and ethnic minority subgroups, compared with the non-Hispanic subgroup. The false-negative rate for Hispanic patients was 12% vs. 3% for non-Hispanic white patients.

Conversely, including race and ethnicity as a predictor of postoperative cancer recurrence improved the model’s accuracy and increased “algorithmic fairness” in terms of calibration slope, discriminative ability, positive predictive value, and false-negative rates. The false-negative rate for Hispanic patients was 9% and 8% for non-Hispanic white patients.

The inclusion of race interaction terms or using race-stratified models did not improve model fairness, likely due to small sample sizes in subgroups, the authors add.
 

‘No one-size-fits-all answer’

“There is no one-size-fits-all answer to whether race/ethnicity should be included, because the health disparity consequences that can result from each clinical decision are different,” Dr. Khor told this news organization.

“The downstream harms and benefits of including or excluding race will need to be carefully considered in each case,” Dr. Khor said.

“When developing a clinical risk prediction algorithm, one should consider the potential racial/ethnic biases present in clinical practice, which translate to bias in the data,” Dr. Khor added. “Care must be taken to think through the implications of such biases during the algorithm development and evaluation process in order to avoid further propagating those biases.”

The coauthors of a linked commentary say this study “highlights current challenges in measuring and addressing algorithmic bias, with implications for both patient care and health policy decision-making.”

Ankur Pandya, PhD, with Harvard School of Public Health, Boston, and Jinyi Zhu, PhD, with Vanderbilt University, Nashville, Tenn., agree that there is no “one-size-fits-all solution” – such as always excluding race and ethnicity from risk models – to confronting algorithmic bias.

“When possible, approaches for identifying and responding to algorithmic bias should focus on the decisions made by patients and policymakers as they relate to the ultimate outcomes of interest (such as length of life, quality of life, and costs) and the distribution of these outcomes across the subgroups that define important health disparities,” Dr. Pandya and Dr. Zhu suggest.

“What is most promising,” they write, is the high level of engagement from researchers, philosophers, policymakers, physicians and other healthcare professionals, caregivers, and patients to this cause in recent years, “suggesting that algorithmic bias will not be left unchecked as access to unprecedented amounts of data and methods continues to increase moving forward.”

This research was supported by a grant from the National Cancer Institute of the National Institutes of Health. The authors and editorial writers have disclosed no relevant financial relationships.

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

CHICAGO – Fewer than 7% of patients newly diagnosed with cancer are tested for germline genetic mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.

The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.

“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.

“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”

Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.

The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.

“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.

They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.

“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.

The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.

Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.

“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.

One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.

“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.

Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
 

Details of the study

Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”

However, “little is known about genetic testing use and results,” Dr. Kurian noted.

The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.

The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.

Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.

Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.

Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.

The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.

By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.

There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.

However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.

The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).

Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.

She also noted that the SEER registries do not collect data on family history or tumor sequencing.

The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.

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

CHICAGO – Fewer than 7% of patients newly diagnosed with cancer are tested for germline genetic mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.

The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.

“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.

“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”

Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.

The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.

“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.

They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.

“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.

The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.

Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.

“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.

One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.

“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.

Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
 

Details of the study

Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”

However, “little is known about genetic testing use and results,” Dr. Kurian noted.

The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.

The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.

Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.

Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.

Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.

The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.

By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.

There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.

However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.

The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).

Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.

She also noted that the SEER registries do not collect data on family history or tumor sequencing.

The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.

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

CHICAGO – Fewer than 7% of patients newly diagnosed with cancer are tested for germline genetic mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.

The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.

“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.

“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”

Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.

The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.

“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.

They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.

“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.

The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.

Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.

“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.

One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.

“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.

Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
 

Details of the study

Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”

However, “little is known about genetic testing use and results,” Dr. Kurian noted.

The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.

The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.

Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.

Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.

Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.

The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.

By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.

There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.

However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.

The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).

Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.

She also noted that the SEER registries do not collect data on family history or tumor sequencing.

The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.

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

TOPLINE:

There may be no threshold dose below which radiation to cardiac substructures does not increase the risk for later cardiac diseases in children with cancer.

METHODOLOGY:

• Review of 25,481 patients in the Childhood Cancer Survivor Study who had no cardiac complications in the first 5 years following cancer treatment from 1970 to 1999; nearly half (48.2%) had been exposed to radiotherapy.
• Radiation doses to the coronary arteries, heart chambers, heart valves, and whole heart were calculated based on radiotherapy records.
• Median age at follow up was 29.8 years and ranged from 5.6 to 65.9 years.

TAKEAWAY:

• Mean radiation doses of 5.0-9.9 Gy to the whole heart did not increase the risk for later cardiac disease.
• Mean doses of 5.0-9.9 Gy to the right coronary artery (rate ratio, 2.6) and left ventricle (RR, 2.2) did increase the risk for subsequent coronary artery disease.
• Mean doses of 5.0-9.9 Gy to the tricuspid valve (RR, 5.5) and right ventricle (RR, 8.4) increased the risk for later valvular disease.
• Linear modeling adequately described the dose-response relationship for many cardiac substructures, suggesting there is no threshold dose necessary for cardiac damage.

IN PRACTICE:

“These findings solidify the need to consider cardiac substructure doses in [pediatric] radiation treatment planning and in survivorship care. Future work to ascertain optimal cardiac dose constraints, especially in the era of highly conformal [radiotherapy] techniques such as [intensity-modulated radiotherapy] and proton therapy, remains critical,” the authors concluded.

STUDY DETAILS:

The study was led by James Bates, MD, of Emory University, Atlanta, and published in the Journal of Clinical Oncology.

LIMITATIONS:

Chronic conditions were self-reported.

Current radiotherapy techniques are much more precise than in the decades when these cancer survivors were treated, allowing preferential sparing of various heart structures.

The study did not assess other treatments and lifestyle issues that may have affected heart health.
 

DISCLOSURES:

The work was funded by the National Cancer Institute. Investigators reported ties to Doximity, Abbott, Merck, Grail, and other companies.

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

TOPLINE:

There may be no threshold dose below which radiation to cardiac substructures does not increase the risk for later cardiac diseases in children with cancer.

METHODOLOGY:

• Review of 25,481 patients in the Childhood Cancer Survivor Study who had no cardiac complications in the first 5 years following cancer treatment from 1970 to 1999; nearly half (48.2%) had been exposed to radiotherapy.
• Radiation doses to the coronary arteries, heart chambers, heart valves, and whole heart were calculated based on radiotherapy records.
• Median age at follow up was 29.8 years and ranged from 5.6 to 65.9 years.

TAKEAWAY:

• Mean radiation doses of 5.0-9.9 Gy to the whole heart did not increase the risk for later cardiac disease.
• Mean doses of 5.0-9.9 Gy to the right coronary artery (rate ratio, 2.6) and left ventricle (RR, 2.2) did increase the risk for subsequent coronary artery disease.
• Mean doses of 5.0-9.9 Gy to the tricuspid valve (RR, 5.5) and right ventricle (RR, 8.4) increased the risk for later valvular disease.
• Linear modeling adequately described the dose-response relationship for many cardiac substructures, suggesting there is no threshold dose necessary for cardiac damage.

IN PRACTICE:

“These findings solidify the need to consider cardiac substructure doses in [pediatric] radiation treatment planning and in survivorship care. Future work to ascertain optimal cardiac dose constraints, especially in the era of highly conformal [radiotherapy] techniques such as [intensity-modulated radiotherapy] and proton therapy, remains critical,” the authors concluded.

STUDY DETAILS:

The study was led by James Bates, MD, of Emory University, Atlanta, and published in the Journal of Clinical Oncology.

LIMITATIONS:

Chronic conditions were self-reported.

Current radiotherapy techniques are much more precise than in the decades when these cancer survivors were treated, allowing preferential sparing of various heart structures.

The study did not assess other treatments and lifestyle issues that may have affected heart health.
 

DISCLOSURES:

The work was funded by the National Cancer Institute. Investigators reported ties to Doximity, Abbott, Merck, Grail, and other companies.

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

TOPLINE:

There may be no threshold dose below which radiation to cardiac substructures does not increase the risk for later cardiac diseases in children with cancer.

METHODOLOGY:

• Review of 25,481 patients in the Childhood Cancer Survivor Study who had no cardiac complications in the first 5 years following cancer treatment from 1970 to 1999; nearly half (48.2%) had been exposed to radiotherapy.
• Radiation doses to the coronary arteries, heart chambers, heart valves, and whole heart were calculated based on radiotherapy records.
• Median age at follow up was 29.8 years and ranged from 5.6 to 65.9 years.

TAKEAWAY:

• Mean radiation doses of 5.0-9.9 Gy to the whole heart did not increase the risk for later cardiac disease.
• Mean doses of 5.0-9.9 Gy to the right coronary artery (rate ratio, 2.6) and left ventricle (RR, 2.2) did increase the risk for subsequent coronary artery disease.
• Mean doses of 5.0-9.9 Gy to the tricuspid valve (RR, 5.5) and right ventricle (RR, 8.4) increased the risk for later valvular disease.
• Linear modeling adequately described the dose-response relationship for many cardiac substructures, suggesting there is no threshold dose necessary for cardiac damage.

IN PRACTICE:

“These findings solidify the need to consider cardiac substructure doses in [pediatric] radiation treatment planning and in survivorship care. Future work to ascertain optimal cardiac dose constraints, especially in the era of highly conformal [radiotherapy] techniques such as [intensity-modulated radiotherapy] and proton therapy, remains critical,” the authors concluded.

STUDY DETAILS:

The study was led by James Bates, MD, of Emory University, Atlanta, and published in the Journal of Clinical Oncology.

LIMITATIONS:

Chronic conditions were self-reported.

Current radiotherapy techniques are much more precise than in the decades when these cancer survivors were treated, allowing preferential sparing of various heart structures.

The study did not assess other treatments and lifestyle issues that may have affected heart health.
 

DISCLOSURES:

The work was funded by the National Cancer Institute. Investigators reported ties to Doximity, Abbott, Merck, Grail, and other companies.

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.

Complications from sickle cell disease (SCD) can affect education and life opportunities, and these complications have been associated with social determinants of health such as socioeconomic status, depression, health literacy, and level of education, according to Kelly M. Harris, PhD, of Washington University in St. Louis, and colleagues.

Pain is a hallmark of SCD, and “the current climate around pain management and opioid use has specific implications for individuals with [SCD], especially youth,” Dr. Harris said in an interview.

In a study published in JAMA Network Open, the researchers analyzed 2,264 participants (average age, 27.9 years; 56.2% were female) in the Sickle Cell Disease Implementation Consortium a study that includes patient assessment, treatment, and creation of a longitudinal registry.

The participants completed the Adult Sickle Cell Quality of Life Measurement Information System to provide data on the frequency and severity of pain episodes related to SCD over the past 12 months. Multivariable regression analysis was used to examine the associations of education, employment, and mental health with pain frequency and severity.

Overall, 79.8% of participants reported severe pain, and 47.8% reported more than four episodes of pain in the past year.

Notably, 20% of the participants were diagnosed with depression, and increased pain frequency was significantly associated with depression, although no significant association appeared between pain severity and depression, the researchers said.

A total of 47% of the participants reported using pain medication and 49% reported using hydroxyurea. In addition, 628 participants (28.0%) underwent regular blood transfusions.

Neither education level nor income was associated with increased pain frequency or severity. Age younger than 18 years was significantly associated with both pain frequency and severity, as was daily used of pain medication. Unemployment and female sex also were associated with increased pain frequency.

The findings were limited by several factors including the cross-sectional design that prevents conclusions of causality, and by the reliance on patient reports of depression, which likely led to underreporting, the researchers noted.

However, the results are consistent with previous studies suggesting that pain and negative feelings were associated with reduced quality of life in SCD patients, especially younger patients, and support the need to screen SCD patients for depression, especially those who report more severe and/or more frequent pain, they said.
 

Take a comprehensive approach to a complex condition

“When treating pain, we cannot just rely on medication,” Dr. Harris said. “It is important that providers consider the full experiences of patients and pursue holistic and comprehensive treatment approaches to reducing pain. Screening for depression should be a regular practice, particularly for patients experiencing frequent and/or severe pain.

“Racial discrimination, stigma, and bias impact pain diagnosis and treatment for individuals with SCD,” said Dr. Harris. “Increasing awareness of the associations between depression and pain frequency and severity ... may help address these barriers.”
 

Data highlight treatment gaps

Alexander A. Boucher, MD, a member of the division of pediatric hematology and oncology at the University of Minnesota, Minneapolis, noted the researchers included patients as young as midadolescence, with a majority being under 35 years old. “The 18- to 30-year-old range is an especially high-risk age window for increased acute health care utilization, even compared with other chronic adolescent/young adult conditions. “The demographics in the study group also reasonably approximate those for young adults with SCD in urban centers. By taking a multicenter approach across a several-state region, I believe the findings offer better generalizability, since health care access and mental health access can vary state-by-state,” and the current results show a more standard experience.

“It was a bit surprising that female [sex] maintained such an association with pain across the different components of the study,” and that the pain peak was in the 25- to 34-year-old age range, said Dr. Boucher. However, anecdotally, the late teens and early 20s “can be laden with mental health concerns due to the life transitions that accompany most people at that time. The note that hydroxyurea use was associated with more pain and depression symptoms was interesting, and serves as a reminder that what is happening to the red blood cells and in the blood vessels, such as red blood cell breakdown, sickling, and vaso-occlusion are only a part of what causes pain, and hydroxyurea is not likely to play a role in mitigating mental health aspects of pain.”

The findings that overall pain frequency and related pain medication use were associated with higher depression rates “may in part reflect a blind spot for physicians and medical teams, who often resort back to physical pain-based heuristics.” Physicians may misunderstand chronic pain and its management and look for quick fixes for pain out of uncertainty or urgency, said Dr. Boucher. “This serves to diminish the perspectives of patients as people first (not embodiments of a disease) and can lead to missed opportunities to tackle mental health challenges.”
 

Barriers and limitations

There are barriers to mental health screening in hematology care,” Dr. Boucher said. First, most hematologists are not experts in mental health and while they may have some from their medical training in these disorders, it can be difficult to maintain the level of health literacy needed to stay up to date on treatments. Second, depression screening may not be part of regular patient intake and the Patient Health Questionnaire–2 or PHQ-9 offer only short-term (2-week) snapshots of depression.

“Perhaps most critically, even if we do successfully screen, the access to mental health specialists is severely limited, just as it is across the medical landscape, so intervention opportunities may be suboptimal,” said Dr. Boucher. The problem is magnified if, as the current study suggests, the rates of depression in SCD are approximately three times greater than the population overall.

In the current study, “the fact that only half of those who self-reported depression symptoms actually had depression documented as a diagnosis in their medical records suggests that we are missing a lot of patients affected by mental health disturbances.”

This study is limited in measurement of the contribution of social determinants of health, he said, as they were primarily focused on employment status and income. The study does not describe other factors like support systems, housing, and transportation.

“I would like to see studies that not only identify associated drivers of pain, but also offer evidence for successful interventions,” Dr. Boucher said, and these studies should include patient-centered interventions versus disease-centered interventions.
 

Undertreatment persists

Other concerns with sickle cell anemia include the underuse of hydroxyurea to reduce complications associated with the disease such as pain, stroke, and even early death. Another recent study in JAMA Network Open suggested that use of hydroxyurea remained low in children and youth despite the issuing of guidelines, and that underserved populations were especially affected. In that study, the researchers found that the patients’ annual days’ supply of hydroxyurea in New York state did not change significantly after the guideline update.

SCD also has been associated with increased risk of other poor outcomes, such as stillbirth and increased risk of poor COVID-19–related outcomes and COVID-19–related deaths.

The study by Dr. Harris and colleagues was supported by the National Institutes of Health through the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. Dr. Harris had no financial conflicts to disclose. The hydroxyurea study was supported by the Agency for Healthcare Research and Quality and the NHLBI. The researchers had no financial conflicts to disclose. Dr. Boucher disclosed conducting research with SCL Behring, but had no relevant financial conflicts.

Complications from sickle cell disease (SCD) can affect education and life opportunities, and these complications have been associated with social determinants of health such as socioeconomic status, depression, health literacy, and level of education, according to Kelly M. Harris, PhD, of Washington University in St. Louis, and colleagues.

Pain is a hallmark of SCD, and “the current climate around pain management and opioid use has specific implications for individuals with [SCD], especially youth,” Dr. Harris said in an interview.

In a study published in JAMA Network Open, the researchers analyzed 2,264 participants (average age, 27.9 years; 56.2% were female) in the Sickle Cell Disease Implementation Consortium a study that includes patient assessment, treatment, and creation of a longitudinal registry.

The participants completed the Adult Sickle Cell Quality of Life Measurement Information System to provide data on the frequency and severity of pain episodes related to SCD over the past 12 months. Multivariable regression analysis was used to examine the associations of education, employment, and mental health with pain frequency and severity.

Overall, 79.8% of participants reported severe pain, and 47.8% reported more than four episodes of pain in the past year.

Notably, 20% of the participants were diagnosed with depression, and increased pain frequency was significantly associated with depression, although no significant association appeared between pain severity and depression, the researchers said.

A total of 47% of the participants reported using pain medication and 49% reported using hydroxyurea. In addition, 628 participants (28.0%) underwent regular blood transfusions.

Neither education level nor income was associated with increased pain frequency or severity. Age younger than 18 years was significantly associated with both pain frequency and severity, as was daily used of pain medication. Unemployment and female sex also were associated with increased pain frequency.

The findings were limited by several factors including the cross-sectional design that prevents conclusions of causality, and by the reliance on patient reports of depression, which likely led to underreporting, the researchers noted.

However, the results are consistent with previous studies suggesting that pain and negative feelings were associated with reduced quality of life in SCD patients, especially younger patients, and support the need to screen SCD patients for depression, especially those who report more severe and/or more frequent pain, they said.
 

Take a comprehensive approach to a complex condition

“When treating pain, we cannot just rely on medication,” Dr. Harris said. “It is important that providers consider the full experiences of patients and pursue holistic and comprehensive treatment approaches to reducing pain. Screening for depression should be a regular practice, particularly for patients experiencing frequent and/or severe pain.

“Racial discrimination, stigma, and bias impact pain diagnosis and treatment for individuals with SCD,” said Dr. Harris. “Increasing awareness of the associations between depression and pain frequency and severity ... may help address these barriers.”
 

Data highlight treatment gaps

Alexander A. Boucher, MD, a member of the division of pediatric hematology and oncology at the University of Minnesota, Minneapolis, noted the researchers included patients as young as midadolescence, with a majority being under 35 years old. “The 18- to 30-year-old range is an especially high-risk age window for increased acute health care utilization, even compared with other chronic adolescent/young adult conditions. “The demographics in the study group also reasonably approximate those for young adults with SCD in urban centers. By taking a multicenter approach across a several-state region, I believe the findings offer better generalizability, since health care access and mental health access can vary state-by-state,” and the current results show a more standard experience.

“It was a bit surprising that female [sex] maintained such an association with pain across the different components of the study,” and that the pain peak was in the 25- to 34-year-old age range, said Dr. Boucher. However, anecdotally, the late teens and early 20s “can be laden with mental health concerns due to the life transitions that accompany most people at that time. The note that hydroxyurea use was associated with more pain and depression symptoms was interesting, and serves as a reminder that what is happening to the red blood cells and in the blood vessels, such as red blood cell breakdown, sickling, and vaso-occlusion are only a part of what causes pain, and hydroxyurea is not likely to play a role in mitigating mental health aspects of pain.”

The findings that overall pain frequency and related pain medication use were associated with higher depression rates “may in part reflect a blind spot for physicians and medical teams, who often resort back to physical pain-based heuristics.” Physicians may misunderstand chronic pain and its management and look for quick fixes for pain out of uncertainty or urgency, said Dr. Boucher. “This serves to diminish the perspectives of patients as people first (not embodiments of a disease) and can lead to missed opportunities to tackle mental health challenges.”
 

Barriers and limitations

There are barriers to mental health screening in hematology care,” Dr. Boucher said. First, most hematologists are not experts in mental health and while they may have some from their medical training in these disorders, it can be difficult to maintain the level of health literacy needed to stay up to date on treatments. Second, depression screening may not be part of regular patient intake and the Patient Health Questionnaire–2 or PHQ-9 offer only short-term (2-week) snapshots of depression.

“Perhaps most critically, even if we do successfully screen, the access to mental health specialists is severely limited, just as it is across the medical landscape, so intervention opportunities may be suboptimal,” said Dr. Boucher. The problem is magnified if, as the current study suggests, the rates of depression in SCD are approximately three times greater than the population overall.

In the current study, “the fact that only half of those who self-reported depression symptoms actually had depression documented as a diagnosis in their medical records suggests that we are missing a lot of patients affected by mental health disturbances.”

This study is limited in measurement of the contribution of social determinants of health, he said, as they were primarily focused on employment status and income. The study does not describe other factors like support systems, housing, and transportation.

“I would like to see studies that not only identify associated drivers of pain, but also offer evidence for successful interventions,” Dr. Boucher said, and these studies should include patient-centered interventions versus disease-centered interventions.
 

Undertreatment persists

Other concerns with sickle cell anemia include the underuse of hydroxyurea to reduce complications associated with the disease such as pain, stroke, and even early death. Another recent study in JAMA Network Open suggested that use of hydroxyurea remained low in children and youth despite the issuing of guidelines, and that underserved populations were especially affected. In that study, the researchers found that the patients’ annual days’ supply of hydroxyurea in New York state did not change significantly after the guideline update.

SCD also has been associated with increased risk of other poor outcomes, such as stillbirth and increased risk of poor COVID-19–related outcomes and COVID-19–related deaths.

The study by Dr. Harris and colleagues was supported by the National Institutes of Health through the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. Dr. Harris had no financial conflicts to disclose. The hydroxyurea study was supported by the Agency for Healthcare Research and Quality and the NHLBI. The researchers had no financial conflicts to disclose. Dr. Boucher disclosed conducting research with SCL Behring, but had no relevant financial conflicts.

Complications from sickle cell disease (SCD) can affect education and life opportunities, and these complications have been associated with social determinants of health such as socioeconomic status, depression, health literacy, and level of education, according to Kelly M. Harris, PhD, of Washington University in St. Louis, and colleagues.

Pain is a hallmark of SCD, and “the current climate around pain management and opioid use has specific implications for individuals with [SCD], especially youth,” Dr. Harris said in an interview.

In a study published in JAMA Network Open, the researchers analyzed 2,264 participants (average age, 27.9 years; 56.2% were female) in the Sickle Cell Disease Implementation Consortium a study that includes patient assessment, treatment, and creation of a longitudinal registry.

The participants completed the Adult Sickle Cell Quality of Life Measurement Information System to provide data on the frequency and severity of pain episodes related to SCD over the past 12 months. Multivariable regression analysis was used to examine the associations of education, employment, and mental health with pain frequency and severity.

Overall, 79.8% of participants reported severe pain, and 47.8% reported more than four episodes of pain in the past year.

Notably, 20% of the participants were diagnosed with depression, and increased pain frequency was significantly associated with depression, although no significant association appeared between pain severity and depression, the researchers said.

A total of 47% of the participants reported using pain medication and 49% reported using hydroxyurea. In addition, 628 participants (28.0%) underwent regular blood transfusions.

Neither education level nor income was associated with increased pain frequency or severity. Age younger than 18 years was significantly associated with both pain frequency and severity, as was daily used of pain medication. Unemployment and female sex also were associated with increased pain frequency.

The findings were limited by several factors including the cross-sectional design that prevents conclusions of causality, and by the reliance on patient reports of depression, which likely led to underreporting, the researchers noted.

However, the results are consistent with previous studies suggesting that pain and negative feelings were associated with reduced quality of life in SCD patients, especially younger patients, and support the need to screen SCD patients for depression, especially those who report more severe and/or more frequent pain, they said.
 

Take a comprehensive approach to a complex condition

“When treating pain, we cannot just rely on medication,” Dr. Harris said. “It is important that providers consider the full experiences of patients and pursue holistic and comprehensive treatment approaches to reducing pain. Screening for depression should be a regular practice, particularly for patients experiencing frequent and/or severe pain.

“Racial discrimination, stigma, and bias impact pain diagnosis and treatment for individuals with SCD,” said Dr. Harris. “Increasing awareness of the associations between depression and pain frequency and severity ... may help address these barriers.”
 

Data highlight treatment gaps

Alexander A. Boucher, MD, a member of the division of pediatric hematology and oncology at the University of Minnesota, Minneapolis, noted the researchers included patients as young as midadolescence, with a majority being under 35 years old. “The 18- to 30-year-old range is an especially high-risk age window for increased acute health care utilization, even compared with other chronic adolescent/young adult conditions. “The demographics in the study group also reasonably approximate those for young adults with SCD in urban centers. By taking a multicenter approach across a several-state region, I believe the findings offer better generalizability, since health care access and mental health access can vary state-by-state,” and the current results show a more standard experience.

“It was a bit surprising that female [sex] maintained such an association with pain across the different components of the study,” and that the pain peak was in the 25- to 34-year-old age range, said Dr. Boucher. However, anecdotally, the late teens and early 20s “can be laden with mental health concerns due to the life transitions that accompany most people at that time. The note that hydroxyurea use was associated with more pain and depression symptoms was interesting, and serves as a reminder that what is happening to the red blood cells and in the blood vessels, such as red blood cell breakdown, sickling, and vaso-occlusion are only a part of what causes pain, and hydroxyurea is not likely to play a role in mitigating mental health aspects of pain.”

The findings that overall pain frequency and related pain medication use were associated with higher depression rates “may in part reflect a blind spot for physicians and medical teams, who often resort back to physical pain-based heuristics.” Physicians may misunderstand chronic pain and its management and look for quick fixes for pain out of uncertainty or urgency, said Dr. Boucher. “This serves to diminish the perspectives of patients as people first (not embodiments of a disease) and can lead to missed opportunities to tackle mental health challenges.”
 

Barriers and limitations

There are barriers to mental health screening in hematology care,” Dr. Boucher said. First, most hematologists are not experts in mental health and while they may have some from their medical training in these disorders, it can be difficult to maintain the level of health literacy needed to stay up to date on treatments. Second, depression screening may not be part of regular patient intake and the Patient Health Questionnaire–2 or PHQ-9 offer only short-term (2-week) snapshots of depression.

“Perhaps most critically, even if we do successfully screen, the access to mental health specialists is severely limited, just as it is across the medical landscape, so intervention opportunities may be suboptimal,” said Dr. Boucher. The problem is magnified if, as the current study suggests, the rates of depression in SCD are approximately three times greater than the population overall.

In the current study, “the fact that only half of those who self-reported depression symptoms actually had depression documented as a diagnosis in their medical records suggests that we are missing a lot of patients affected by mental health disturbances.”

This study is limited in measurement of the contribution of social determinants of health, he said, as they were primarily focused on employment status and income. The study does not describe other factors like support systems, housing, and transportation.

“I would like to see studies that not only identify associated drivers of pain, but also offer evidence for successful interventions,” Dr. Boucher said, and these studies should include patient-centered interventions versus disease-centered interventions.
 

Undertreatment persists

Other concerns with sickle cell anemia include the underuse of hydroxyurea to reduce complications associated with the disease such as pain, stroke, and even early death. Another recent study in JAMA Network Open suggested that use of hydroxyurea remained low in children and youth despite the issuing of guidelines, and that underserved populations were especially affected. In that study, the researchers found that the patients’ annual days’ supply of hydroxyurea in New York state did not change significantly after the guideline update.

SCD also has been associated with increased risk of other poor outcomes, such as stillbirth and increased risk of poor COVID-19–related outcomes and COVID-19–related deaths.

The study by Dr. Harris and colleagues was supported by the National Institutes of Health through the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. Dr. Harris had no financial conflicts to disclose. The hydroxyurea study was supported by the Agency for Healthcare Research and Quality and the NHLBI. The researchers had no financial conflicts to disclose. Dr. Boucher disclosed conducting research with SCL Behring, but had no relevant financial conflicts.