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Hepatic infusion pumps: New enthusiasm for an old technology

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Mon, 02/12/2024 - 12:02

Renewed interest in hepatic arterial chemotherapy infusion pumps may be on the horizon, given promising overall survival findings in patients with advanced, unresectable cholangiocarcinoma.

Dutch investigators reported a 3-year overall survival of 33% in patients with advanced, unresectable cholangiocarcinoma confined to the liver who received the infusion chemotherapy vs 3% in historical controls treated with standard systemic gemcitabine/cisplatin.

The response with the pump is “clearly superior” to systemic treatment, said investigator Bas Groot Koerkamp, MD, who presented the findings at the ASCO Gastrointestinal Cancers Symposium.

“I do share the enthusiasm of my colleagues about immunotherapy and targeted treatments for intrahepatic cholangiocarcinoma,” said Dr. Koerkamp, a hepato-pancreato-biliary surgeon at Erasmus University Medical Center, Rotterdam, the Netherlands. But “none of these treatments has shown a 3-year overall survival of one in three with advanced disease.”

The hepatic arterial infusion pump, a hockey puck-sized device that essentially bathes liver tumors in floxuridine for about 2 weeks, is not a new technology. The pump has been around since at least the 1990s, developed largely at Memorial Sloan Kettering Cancer Center, New York City, where Dr. Koerkamp trained.

Three previous small studies in cholangiocarcinoma reported outcomes similar to Dr. Koerkamp’s. Despite the strong survival outcomes, uptake of these pumps has lagged.

A key reason is likely the lack of phase 3 trials evaluating the technology, Laleh Melstrom, MD, chief of surgical oncology at City of Hope, outside of Los Angeles, Duarte, California, told this news organization.

Dr. Melstrom, who moderated Dr. Koerkamp’s presentation, also noted that using the pump requires special attention to bilirubin levels to prevent biliary toxicity and knowledge of pump placement.

The pump, placed subcutaneously on one side of the lower abdomen, is connected to a side branch of the hepatic artery and then filled with the chemotherapy agent floxuridine. Delivering floxuridine directly to the hepatic artery increases liver lesion exposure 200-fold over systemic delivery. The pump needs to be refilled after 2 weeks.

“It’s not difficult to place the pump, even doing it robotically,” which was how it was placed in over 40% of patients in the study, Dr. Koerkamp said.

As for biliary toxicity, only one patient in the current study developed biliary sclerosis, which was easily handled with a stent. “You just put in a stent and continue,” Dr. Koerkamp said.

The current single-arm phase 2 study included 50 patients implanted with the hepatic pump at three centers in the Netherlands. All patients had advanced, unresectable cholangiocarcinoma confined to the liver.

Ultimately, 48 of 50 patients received treatment after one patient died of unrelated causes and another had an arterial dissection.

Overall, 38 received gemcitabine/cisplatin concurrently, and the remaining had the pump treatment alone, having already received the systemic combination. Most (84%) received at least four cycles of chemotherapy infusion.

Almost half of patients (46%) had a partial response to treatment, and 88% exhibited disease control at 6 months. Four patients who responded underwent a liver resection, one of whom had a complete pathologic response.

Median overall survival was 22 months vs 12 months in historical controls. One-year median overall survival was 80% in the treatment group vs 47% in controls, and 3-year median overall survival was 33% in the pump group vs 3% in controls.

An audience member noted that similar results have been reported for transarterial Yttrium-90 radioembolization, another and newer option to treat intrahepatic cholangiocarcinoma.

“The Y90 results are quite impressive,” Dr. Koerkamp said, adding that he’d like to see a head-to-head comparison.

“The main advantage of the pump is that it treats the entire liver,” as opposed to one lesion at a time, “so if you have 10 lesions [the pump] makes a lot more sense,” he said.

There is “definitely a movement” to “reinvigorate” the hepatic artery infusion pump approach, Dr. Melstrom said.

The study was funded by the Dutch Cancer Society. Dr. Koerkamp disclosed research funding from Tricumed, a maker of implantable infusion pumps. Dr. Melstrom didn’t have any disclosures.

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

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Renewed interest in hepatic arterial chemotherapy infusion pumps may be on the horizon, given promising overall survival findings in patients with advanced, unresectable cholangiocarcinoma.

Dutch investigators reported a 3-year overall survival of 33% in patients with advanced, unresectable cholangiocarcinoma confined to the liver who received the infusion chemotherapy vs 3% in historical controls treated with standard systemic gemcitabine/cisplatin.

The response with the pump is “clearly superior” to systemic treatment, said investigator Bas Groot Koerkamp, MD, who presented the findings at the ASCO Gastrointestinal Cancers Symposium.

“I do share the enthusiasm of my colleagues about immunotherapy and targeted treatments for intrahepatic cholangiocarcinoma,” said Dr. Koerkamp, a hepato-pancreato-biliary surgeon at Erasmus University Medical Center, Rotterdam, the Netherlands. But “none of these treatments has shown a 3-year overall survival of one in three with advanced disease.”

The hepatic arterial infusion pump, a hockey puck-sized device that essentially bathes liver tumors in floxuridine for about 2 weeks, is not a new technology. The pump has been around since at least the 1990s, developed largely at Memorial Sloan Kettering Cancer Center, New York City, where Dr. Koerkamp trained.

Three previous small studies in cholangiocarcinoma reported outcomes similar to Dr. Koerkamp’s. Despite the strong survival outcomes, uptake of these pumps has lagged.

A key reason is likely the lack of phase 3 trials evaluating the technology, Laleh Melstrom, MD, chief of surgical oncology at City of Hope, outside of Los Angeles, Duarte, California, told this news organization.

Dr. Melstrom, who moderated Dr. Koerkamp’s presentation, also noted that using the pump requires special attention to bilirubin levels to prevent biliary toxicity and knowledge of pump placement.

The pump, placed subcutaneously on one side of the lower abdomen, is connected to a side branch of the hepatic artery and then filled with the chemotherapy agent floxuridine. Delivering floxuridine directly to the hepatic artery increases liver lesion exposure 200-fold over systemic delivery. The pump needs to be refilled after 2 weeks.

“It’s not difficult to place the pump, even doing it robotically,” which was how it was placed in over 40% of patients in the study, Dr. Koerkamp said.

As for biliary toxicity, only one patient in the current study developed biliary sclerosis, which was easily handled with a stent. “You just put in a stent and continue,” Dr. Koerkamp said.

The current single-arm phase 2 study included 50 patients implanted with the hepatic pump at three centers in the Netherlands. All patients had advanced, unresectable cholangiocarcinoma confined to the liver.

Ultimately, 48 of 50 patients received treatment after one patient died of unrelated causes and another had an arterial dissection.

Overall, 38 received gemcitabine/cisplatin concurrently, and the remaining had the pump treatment alone, having already received the systemic combination. Most (84%) received at least four cycles of chemotherapy infusion.

Almost half of patients (46%) had a partial response to treatment, and 88% exhibited disease control at 6 months. Four patients who responded underwent a liver resection, one of whom had a complete pathologic response.

Median overall survival was 22 months vs 12 months in historical controls. One-year median overall survival was 80% in the treatment group vs 47% in controls, and 3-year median overall survival was 33% in the pump group vs 3% in controls.

An audience member noted that similar results have been reported for transarterial Yttrium-90 radioembolization, another and newer option to treat intrahepatic cholangiocarcinoma.

“The Y90 results are quite impressive,” Dr. Koerkamp said, adding that he’d like to see a head-to-head comparison.

“The main advantage of the pump is that it treats the entire liver,” as opposed to one lesion at a time, “so if you have 10 lesions [the pump] makes a lot more sense,” he said.

There is “definitely a movement” to “reinvigorate” the hepatic artery infusion pump approach, Dr. Melstrom said.

The study was funded by the Dutch Cancer Society. Dr. Koerkamp disclosed research funding from Tricumed, a maker of implantable infusion pumps. Dr. Melstrom didn’t have any disclosures.

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

Renewed interest in hepatic arterial chemotherapy infusion pumps may be on the horizon, given promising overall survival findings in patients with advanced, unresectable cholangiocarcinoma.

Dutch investigators reported a 3-year overall survival of 33% in patients with advanced, unresectable cholangiocarcinoma confined to the liver who received the infusion chemotherapy vs 3% in historical controls treated with standard systemic gemcitabine/cisplatin.

The response with the pump is “clearly superior” to systemic treatment, said investigator Bas Groot Koerkamp, MD, who presented the findings at the ASCO Gastrointestinal Cancers Symposium.

“I do share the enthusiasm of my colleagues about immunotherapy and targeted treatments for intrahepatic cholangiocarcinoma,” said Dr. Koerkamp, a hepato-pancreato-biliary surgeon at Erasmus University Medical Center, Rotterdam, the Netherlands. But “none of these treatments has shown a 3-year overall survival of one in three with advanced disease.”

The hepatic arterial infusion pump, a hockey puck-sized device that essentially bathes liver tumors in floxuridine for about 2 weeks, is not a new technology. The pump has been around since at least the 1990s, developed largely at Memorial Sloan Kettering Cancer Center, New York City, where Dr. Koerkamp trained.

Three previous small studies in cholangiocarcinoma reported outcomes similar to Dr. Koerkamp’s. Despite the strong survival outcomes, uptake of these pumps has lagged.

A key reason is likely the lack of phase 3 trials evaluating the technology, Laleh Melstrom, MD, chief of surgical oncology at City of Hope, outside of Los Angeles, Duarte, California, told this news organization.

Dr. Melstrom, who moderated Dr. Koerkamp’s presentation, also noted that using the pump requires special attention to bilirubin levels to prevent biliary toxicity and knowledge of pump placement.

The pump, placed subcutaneously on one side of the lower abdomen, is connected to a side branch of the hepatic artery and then filled with the chemotherapy agent floxuridine. Delivering floxuridine directly to the hepatic artery increases liver lesion exposure 200-fold over systemic delivery. The pump needs to be refilled after 2 weeks.

“It’s not difficult to place the pump, even doing it robotically,” which was how it was placed in over 40% of patients in the study, Dr. Koerkamp said.

As for biliary toxicity, only one patient in the current study developed biliary sclerosis, which was easily handled with a stent. “You just put in a stent and continue,” Dr. Koerkamp said.

The current single-arm phase 2 study included 50 patients implanted with the hepatic pump at three centers in the Netherlands. All patients had advanced, unresectable cholangiocarcinoma confined to the liver.

Ultimately, 48 of 50 patients received treatment after one patient died of unrelated causes and another had an arterial dissection.

Overall, 38 received gemcitabine/cisplatin concurrently, and the remaining had the pump treatment alone, having already received the systemic combination. Most (84%) received at least four cycles of chemotherapy infusion.

Almost half of patients (46%) had a partial response to treatment, and 88% exhibited disease control at 6 months. Four patients who responded underwent a liver resection, one of whom had a complete pathologic response.

Median overall survival was 22 months vs 12 months in historical controls. One-year median overall survival was 80% in the treatment group vs 47% in controls, and 3-year median overall survival was 33% in the pump group vs 3% in controls.

An audience member noted that similar results have been reported for transarterial Yttrium-90 radioembolization, another and newer option to treat intrahepatic cholangiocarcinoma.

“The Y90 results are quite impressive,” Dr. Koerkamp said, adding that he’d like to see a head-to-head comparison.

“The main advantage of the pump is that it treats the entire liver,” as opposed to one lesion at a time, “so if you have 10 lesions [the pump] makes a lot more sense,” he said.

There is “definitely a movement” to “reinvigorate” the hepatic artery infusion pump approach, Dr. Melstrom said.

The study was funded by the Dutch Cancer Society. Dr. Koerkamp disclosed research funding from Tricumed, a maker of implantable infusion pumps. Dr. Melstrom didn’t have any disclosures.

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

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Targeted Colorectal Cancer Combo Improves QoL

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Tue, 02/06/2024 - 16:23

In patients with colorectal cancer bearing the KRAS G12C mutation, a combination of the Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C inhibitor sotorasib and the epidermal growth factor receptor inhibitor panitumumab led to an improvement in quality of life (QoL) measures compared with standard therapy.

Dominik Modest, MD, presented these new results of the phase 3 CodeBreaK 300 trial at the 2024 ASCO Gastrointestinal Cancers Symposium.

The KRAS G12C mutation occurs in 3%-4% of metastatic colorectal cancer cases, according to Dr. Modest and the other authors of a paper published in the New England Journal of Medicine describing the primary outcome of the trial. The study included 160 patients who were randomized to once daily sotorasib (960 mg) plus panitumumab (Soto960), once daily sotorasib (240 mg) plus panitumumab (Soto240), or investigator’s choice of trifluridine–tipiracil or regorafenib.

The December 2023 paper described improvements in median progression-free survival, progression or death, and objective response (OR). The authors described statistically significant improvements in disease progression or death in the Soto960 group (hazard ratio [HR], 0.49; P = .006) and the Soto240 group (HR, 0.58; P = .03). The objective response rate was highest in the Soto960 group (26.4%; 95% CI, 15.3%-40.3%), followed by the Soto240 group (5.7%; 95% CI, 1.2%-15.7%), and the control group (0%; 95% CI, 0.0%-6.6%). Grade 3 or higher treatment-related adverse events were generally similar at 35.8% (Soto960), 30.2% (Soto240), and 43.1% (control) in each group. The most common adverse events associated with sotorasib-panitumumab were skin-related toxicity and hypomagnesemia.

The new analysis showed that both doses of sotorasib also improved patient-reported outcomes from baseline to week 8, Dr. Modest, professor of medicine at Charité University of Medicine in Berlin, said at the meeting.

Compared with the chemotherapy group, there were statistically significant differences in least square mean change from baseline to week 8 for: pain at its worst in the Soto240 group (Brief Pain Inventory [BPI], –1.18; 95% CI, –2.05 to –0.32) and the Soto960 group (BPI, –1.49; 95% CI, –2.36 to –0.61); and physical functioning, as measured by the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire, in the Soto240 (7.95; 95% CI, 2.39-13.51) and Soto960 (6.73; 95% CI, 1.05-12.41) groups. Nearly all other measures trended toward favoring the sotorasib/panitumumab groups, but did not reach statistical significance. A similar pattern was seen in time to deterioration measures. Among adverse events, diarrhea trended toward being more frequent in the intervention arms.

At week 9, 63% of patients in Soto960 and 84% in Soto240 reported improvement in the Patient Global Impression of Change score (PGI-C), versus 37% in the chemotherapy arm. At week 17, the percentages were 77%, 59%, and 21%, respectively.

“The clinical benefits and the better quality of life outcomes associated with sotorasib at the high dose of 960 milligrams plus panitumumab establishes this combination as a potential new standard [therapy] for patients with chemorefractory KRAS G12C mutant colorectal cancer, and I think it’s quite reassuring that even if you compare two active drugs versus one active drug, this does not necessarily translate into impaired quality of life assessments by the patients,” Dr. Modest said during his presentation.

CodeBreaK 300 may point the way to other dual therapies involving kinase inhibitors, according to Rona Yaeger, MD, who wrote an accompanying editorial to the NEJM paper. Dr. Yaeger noted that clinical and preclinical studies had shown that targeted oncogenes like KRAS G12C and BRAF V600E alone would be insufficient in colorectal cancer.

When combined with KRAS G12C inhibitors, EGFR inhibitors prevent EGFR from participating in negative feedback loops that can otherwise lead to drug resistance. “Whether targeting [receptor tyrosine kinases like EGFR] in epithelial tumors other than those associated with colorectal cancers would improve the incidence of response to KRAS G12C inhibitors remains unknown,” wrote Dr. Yaeger, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. There is an ongoing clinical trial evaluating KRAS G12C inhibitors combined with EGFR antibodies in both lung and pancreatic cancer.

She noted that colorectal tumors have high levels of receptor tyrosine kinases, and argued that this will require higher doses of KRAS G12C inhibitors or novel drugs with higher activity. This is supported by the higher frequency of response and longer PFS at the higher dose in CodeBreaK 300, but could present a challenge: “Lowering the drug dose to manage toxic effects may limit the efficacy of the drug against some cancers,” she wrote.

Dr. Yaeger highlighted the KRYSTAL-10 phase 3 randomized trial, which is assessing the KRAS G12C inhibitor adagrasib in combination with the EGFR antibody cetuximab versus chemotherapy in advanced solid tumors with the KRAS G12C mutation.

“The CodeBreaK 300 trial is an exciting first step for targeting KRAS in colorectal cancer,” Dr. Yaeger wrote.

Dr. Modest has financial relationships with Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, Incyte, Lily, Merck Serono, Merck Sharp & Dohme, Onkowissen, Pierre Fabre, Roche, and SERVIER. Dr. Yaeger has financial relationships with Amgen, Boehringer Ingelheim, Daiichi Sankyo, Mirati, Pfizer, and Zai Lab.

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In patients with colorectal cancer bearing the KRAS G12C mutation, a combination of the Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C inhibitor sotorasib and the epidermal growth factor receptor inhibitor panitumumab led to an improvement in quality of life (QoL) measures compared with standard therapy.

Dominik Modest, MD, presented these new results of the phase 3 CodeBreaK 300 trial at the 2024 ASCO Gastrointestinal Cancers Symposium.

The KRAS G12C mutation occurs in 3%-4% of metastatic colorectal cancer cases, according to Dr. Modest and the other authors of a paper published in the New England Journal of Medicine describing the primary outcome of the trial. The study included 160 patients who were randomized to once daily sotorasib (960 mg) plus panitumumab (Soto960), once daily sotorasib (240 mg) plus panitumumab (Soto240), or investigator’s choice of trifluridine–tipiracil or regorafenib.

The December 2023 paper described improvements in median progression-free survival, progression or death, and objective response (OR). The authors described statistically significant improvements in disease progression or death in the Soto960 group (hazard ratio [HR], 0.49; P = .006) and the Soto240 group (HR, 0.58; P = .03). The objective response rate was highest in the Soto960 group (26.4%; 95% CI, 15.3%-40.3%), followed by the Soto240 group (5.7%; 95% CI, 1.2%-15.7%), and the control group (0%; 95% CI, 0.0%-6.6%). Grade 3 or higher treatment-related adverse events were generally similar at 35.8% (Soto960), 30.2% (Soto240), and 43.1% (control) in each group. The most common adverse events associated with sotorasib-panitumumab were skin-related toxicity and hypomagnesemia.

The new analysis showed that both doses of sotorasib also improved patient-reported outcomes from baseline to week 8, Dr. Modest, professor of medicine at Charité University of Medicine in Berlin, said at the meeting.

Compared with the chemotherapy group, there were statistically significant differences in least square mean change from baseline to week 8 for: pain at its worst in the Soto240 group (Brief Pain Inventory [BPI], –1.18; 95% CI, –2.05 to –0.32) and the Soto960 group (BPI, –1.49; 95% CI, –2.36 to –0.61); and physical functioning, as measured by the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire, in the Soto240 (7.95; 95% CI, 2.39-13.51) and Soto960 (6.73; 95% CI, 1.05-12.41) groups. Nearly all other measures trended toward favoring the sotorasib/panitumumab groups, but did not reach statistical significance. A similar pattern was seen in time to deterioration measures. Among adverse events, diarrhea trended toward being more frequent in the intervention arms.

At week 9, 63% of patients in Soto960 and 84% in Soto240 reported improvement in the Patient Global Impression of Change score (PGI-C), versus 37% in the chemotherapy arm. At week 17, the percentages were 77%, 59%, and 21%, respectively.

“The clinical benefits and the better quality of life outcomes associated with sotorasib at the high dose of 960 milligrams plus panitumumab establishes this combination as a potential new standard [therapy] for patients with chemorefractory KRAS G12C mutant colorectal cancer, and I think it’s quite reassuring that even if you compare two active drugs versus one active drug, this does not necessarily translate into impaired quality of life assessments by the patients,” Dr. Modest said during his presentation.

CodeBreaK 300 may point the way to other dual therapies involving kinase inhibitors, according to Rona Yaeger, MD, who wrote an accompanying editorial to the NEJM paper. Dr. Yaeger noted that clinical and preclinical studies had shown that targeted oncogenes like KRAS G12C and BRAF V600E alone would be insufficient in colorectal cancer.

When combined with KRAS G12C inhibitors, EGFR inhibitors prevent EGFR from participating in negative feedback loops that can otherwise lead to drug resistance. “Whether targeting [receptor tyrosine kinases like EGFR] in epithelial tumors other than those associated with colorectal cancers would improve the incidence of response to KRAS G12C inhibitors remains unknown,” wrote Dr. Yaeger, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. There is an ongoing clinical trial evaluating KRAS G12C inhibitors combined with EGFR antibodies in both lung and pancreatic cancer.

She noted that colorectal tumors have high levels of receptor tyrosine kinases, and argued that this will require higher doses of KRAS G12C inhibitors or novel drugs with higher activity. This is supported by the higher frequency of response and longer PFS at the higher dose in CodeBreaK 300, but could present a challenge: “Lowering the drug dose to manage toxic effects may limit the efficacy of the drug against some cancers,” she wrote.

Dr. Yaeger highlighted the KRYSTAL-10 phase 3 randomized trial, which is assessing the KRAS G12C inhibitor adagrasib in combination with the EGFR antibody cetuximab versus chemotherapy in advanced solid tumors with the KRAS G12C mutation.

“The CodeBreaK 300 trial is an exciting first step for targeting KRAS in colorectal cancer,” Dr. Yaeger wrote.

Dr. Modest has financial relationships with Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, Incyte, Lily, Merck Serono, Merck Sharp & Dohme, Onkowissen, Pierre Fabre, Roche, and SERVIER. Dr. Yaeger has financial relationships with Amgen, Boehringer Ingelheim, Daiichi Sankyo, Mirati, Pfizer, and Zai Lab.

In patients with colorectal cancer bearing the KRAS G12C mutation, a combination of the Kirsten rat sarcoma viral oncogene homologue (KRAS) G12C inhibitor sotorasib and the epidermal growth factor receptor inhibitor panitumumab led to an improvement in quality of life (QoL) measures compared with standard therapy.

Dominik Modest, MD, presented these new results of the phase 3 CodeBreaK 300 trial at the 2024 ASCO Gastrointestinal Cancers Symposium.

The KRAS G12C mutation occurs in 3%-4% of metastatic colorectal cancer cases, according to Dr. Modest and the other authors of a paper published in the New England Journal of Medicine describing the primary outcome of the trial. The study included 160 patients who were randomized to once daily sotorasib (960 mg) plus panitumumab (Soto960), once daily sotorasib (240 mg) plus panitumumab (Soto240), or investigator’s choice of trifluridine–tipiracil or regorafenib.

The December 2023 paper described improvements in median progression-free survival, progression or death, and objective response (OR). The authors described statistically significant improvements in disease progression or death in the Soto960 group (hazard ratio [HR], 0.49; P = .006) and the Soto240 group (HR, 0.58; P = .03). The objective response rate was highest in the Soto960 group (26.4%; 95% CI, 15.3%-40.3%), followed by the Soto240 group (5.7%; 95% CI, 1.2%-15.7%), and the control group (0%; 95% CI, 0.0%-6.6%). Grade 3 or higher treatment-related adverse events were generally similar at 35.8% (Soto960), 30.2% (Soto240), and 43.1% (control) in each group. The most common adverse events associated with sotorasib-panitumumab were skin-related toxicity and hypomagnesemia.

The new analysis showed that both doses of sotorasib also improved patient-reported outcomes from baseline to week 8, Dr. Modest, professor of medicine at Charité University of Medicine in Berlin, said at the meeting.

Compared with the chemotherapy group, there were statistically significant differences in least square mean change from baseline to week 8 for: pain at its worst in the Soto240 group (Brief Pain Inventory [BPI], –1.18; 95% CI, –2.05 to –0.32) and the Soto960 group (BPI, –1.49; 95% CI, –2.36 to –0.61); and physical functioning, as measured by the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire, in the Soto240 (7.95; 95% CI, 2.39-13.51) and Soto960 (6.73; 95% CI, 1.05-12.41) groups. Nearly all other measures trended toward favoring the sotorasib/panitumumab groups, but did not reach statistical significance. A similar pattern was seen in time to deterioration measures. Among adverse events, diarrhea trended toward being more frequent in the intervention arms.

At week 9, 63% of patients in Soto960 and 84% in Soto240 reported improvement in the Patient Global Impression of Change score (PGI-C), versus 37% in the chemotherapy arm. At week 17, the percentages were 77%, 59%, and 21%, respectively.

“The clinical benefits and the better quality of life outcomes associated with sotorasib at the high dose of 960 milligrams plus panitumumab establishes this combination as a potential new standard [therapy] for patients with chemorefractory KRAS G12C mutant colorectal cancer, and I think it’s quite reassuring that even if you compare two active drugs versus one active drug, this does not necessarily translate into impaired quality of life assessments by the patients,” Dr. Modest said during his presentation.

CodeBreaK 300 may point the way to other dual therapies involving kinase inhibitors, according to Rona Yaeger, MD, who wrote an accompanying editorial to the NEJM paper. Dr. Yaeger noted that clinical and preclinical studies had shown that targeted oncogenes like KRAS G12C and BRAF V600E alone would be insufficient in colorectal cancer.

When combined with KRAS G12C inhibitors, EGFR inhibitors prevent EGFR from participating in negative feedback loops that can otherwise lead to drug resistance. “Whether targeting [receptor tyrosine kinases like EGFR] in epithelial tumors other than those associated with colorectal cancers would improve the incidence of response to KRAS G12C inhibitors remains unknown,” wrote Dr. Yaeger, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. There is an ongoing clinical trial evaluating KRAS G12C inhibitors combined with EGFR antibodies in both lung and pancreatic cancer.

She noted that colorectal tumors have high levels of receptor tyrosine kinases, and argued that this will require higher doses of KRAS G12C inhibitors or novel drugs with higher activity. This is supported by the higher frequency of response and longer PFS at the higher dose in CodeBreaK 300, but could present a challenge: “Lowering the drug dose to manage toxic effects may limit the efficacy of the drug against some cancers,” she wrote.

Dr. Yaeger highlighted the KRYSTAL-10 phase 3 randomized trial, which is assessing the KRAS G12C inhibitor adagrasib in combination with the EGFR antibody cetuximab versus chemotherapy in advanced solid tumors with the KRAS G12C mutation.

“The CodeBreaK 300 trial is an exciting first step for targeting KRAS in colorectal cancer,” Dr. Yaeger wrote.

Dr. Modest has financial relationships with Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, Incyte, Lily, Merck Serono, Merck Sharp & Dohme, Onkowissen, Pierre Fabre, Roche, and SERVIER. Dr. Yaeger has financial relationships with Amgen, Boehringer Ingelheim, Daiichi Sankyo, Mirati, Pfizer, and Zai Lab.

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Immunotherapy Combo Wins Big on PFS in First-Line Mets CRC

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Tue, 02/06/2024 - 16:26

SAN FRANCISCO — The immunotherapy combination nivolumab plus ipilimumab rivals chemotherapy as well as pembrolizumab monotherapy in the first-line treatment of metastatic colorectal cancer (CRC), new data indicated.

Findings from the CHECKMATE-8HW trial revealed that first-line nivolumab plus ipilimumab led to a significant improvement in progression-free survival (PFS) compared with chemotherapy among patients with metastatic CRC.

More specifically, at 2 years, PFS was 72% among patients with microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) randomized to the immunotherapy combination compared with just 14% among those randomized to chemotherapy with or without targeted therapy.

The magnitude of the benefit was unexpected, especially considering patients received only four cycles of the immunotherapy combination in the trial. “It’s a good surprise,” said lead investigator Thierry Andre, MD, who presented the findings at the 2024 ASCO Gastrointestinal Cancers Symposium.

The findings indicate that nivolumab plus ipilimumab should really be “a new standard,” said Andre, a medical oncologist at Sorbonne University, Paris.

The combination as well as nivolumab alone has received US Food and Drug Administration’s (FDA’s) approval to treat MSI-H or dMMR metastatic CRC in the second line, following chemotherapy failure.

The FDA also approved pembrolizumab as first-line monotherapy for this CRC indication in 2020. The KEYNOTE-177 trial, which led to the pembrolizumab approval, reported a 2-year PFS of 48% among patients receiving the monotherapy. Andre was the lead investigator on KEYNOTE-177.

To compare PFS results for pembrolizumab and nivolumab alone, the CHECKMATE-8HW trial included a nivolumab monotherapy arm, but these results are pending, as are the overall survival findings, Andre said.

Overall, CHECKMATE-8HW must be taken into context with KEYNOTE-177, and “we need a little bit more trial data” for oncologists to decide between the two options, said Neil Newman, MD, a radiation oncologist at the University of Texas Health Science Center, San Antonio, Texas, who co-moderated Dr. Andre’s presentation.

Andre noted, however, that if the nivolumab and pembrolizumab monotherapy results are similar, most patients will likely receive the nivolumab/ipilimumab combination, given the improved PFS outcomes.

In CHECKMATE-8HW, patients were randomized to three regimens. The 202 patients in the combination arm received nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. The 101 patients in the chemotherapy group received investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab. And the nivolumab monotherapy arm received nivolumab 240 mg every 2 weeks for six doses, followed by nivolumab 480 mg every 4 weeks.

Treatment continued until disease progression or unacceptable toxicity over a maximum of 2 years. The median duration of treatment was 13.5 months in the nivolumab/ipilimumab arm vs 4 months in the chemotherapy arm.

PFS curves started to separate between nivolumab/ipilimumab and chemotherapy at about 3 months.

Patients receiving the combination exhibited a 79% reduction in the risk for disease progression or death at 2 years (72% vs 14%; hazard ratio, 0.21; P < .0001). The median PFS was not reached with the combination vs 5.9 months with chemotherapy. The PFS benefit of nivolumab/ipilimumab held across various subgroups, including patients with KRAS or NRAS mutations and baseline lung, liver, or peritoneal metastases.

The incidence of grade 3/4 treatment-related adverse events was 23% with nivolumab/ipilimumab vs 48% in the chemotherapy arm. The most common grade 3/4 events with nivolumab/ipilimumab were diarrhea/colitis (5%), adrenal insufficiency (4%), hepatitis (3%), and inflammation of the pituitary gland (3%).

Two treatment-related deaths occurred in the combination arm — one from pneumonitis and the second from myocarditis — and none occurred in the chemotherapy arm.

Mark A. Lewis, MD, a gastrointestinal oncologist at Intermountain Healthcare in Murray, Utah, was impressed with the CHECKMATE-8HW findings. The data are shaping up to make nivolumab/ipilimumab “the next great step in metastatic CRC management beyond KEYNOTE-177,” Dr. Lewis said.

Dr. Lewis noted that the new trial makes it “imperative” to standardize testing for immunotherapy candidacy upfront. “It is completely unacceptable for any patient with metastatic CRC to not have their MMR/MSI status assessed,” he said. “Much as no oncologist would dare treat breast cancer without testing ER, PR, HER2 status, biomarkers cannot be a later-line afterthought in stage IV CRC.”

Drugmaker Bristol-Myers Squibb told this news organization that the company will be seeking a first-line indication for the combination, and anticipates approval early next year or possibly sooner, if the FDA grants a priority review.

The work was funded by Bristol-Myers Squibb and the ONO Pharmaceutical Company. Dr. Andre had numerous industry ties, including being a consultant for both BMS and Merck. He also reported honoraria from both companies. Dr. Newman and Dr. Lewis didn’t have any disclosures.

A version of this article appeared on Medscape.com.

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SAN FRANCISCO — The immunotherapy combination nivolumab plus ipilimumab rivals chemotherapy as well as pembrolizumab monotherapy in the first-line treatment of metastatic colorectal cancer (CRC), new data indicated.

Findings from the CHECKMATE-8HW trial revealed that first-line nivolumab plus ipilimumab led to a significant improvement in progression-free survival (PFS) compared with chemotherapy among patients with metastatic CRC.

More specifically, at 2 years, PFS was 72% among patients with microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) randomized to the immunotherapy combination compared with just 14% among those randomized to chemotherapy with or without targeted therapy.

The magnitude of the benefit was unexpected, especially considering patients received only four cycles of the immunotherapy combination in the trial. “It’s a good surprise,” said lead investigator Thierry Andre, MD, who presented the findings at the 2024 ASCO Gastrointestinal Cancers Symposium.

The findings indicate that nivolumab plus ipilimumab should really be “a new standard,” said Andre, a medical oncologist at Sorbonne University, Paris.

The combination as well as nivolumab alone has received US Food and Drug Administration’s (FDA’s) approval to treat MSI-H or dMMR metastatic CRC in the second line, following chemotherapy failure.

The FDA also approved pembrolizumab as first-line monotherapy for this CRC indication in 2020. The KEYNOTE-177 trial, which led to the pembrolizumab approval, reported a 2-year PFS of 48% among patients receiving the monotherapy. Andre was the lead investigator on KEYNOTE-177.

To compare PFS results for pembrolizumab and nivolumab alone, the CHECKMATE-8HW trial included a nivolumab monotherapy arm, but these results are pending, as are the overall survival findings, Andre said.

Overall, CHECKMATE-8HW must be taken into context with KEYNOTE-177, and “we need a little bit more trial data” for oncologists to decide between the two options, said Neil Newman, MD, a radiation oncologist at the University of Texas Health Science Center, San Antonio, Texas, who co-moderated Dr. Andre’s presentation.

Andre noted, however, that if the nivolumab and pembrolizumab monotherapy results are similar, most patients will likely receive the nivolumab/ipilimumab combination, given the improved PFS outcomes.

In CHECKMATE-8HW, patients were randomized to three regimens. The 202 patients in the combination arm received nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. The 101 patients in the chemotherapy group received investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab. And the nivolumab monotherapy arm received nivolumab 240 mg every 2 weeks for six doses, followed by nivolumab 480 mg every 4 weeks.

Treatment continued until disease progression or unacceptable toxicity over a maximum of 2 years. The median duration of treatment was 13.5 months in the nivolumab/ipilimumab arm vs 4 months in the chemotherapy arm.

PFS curves started to separate between nivolumab/ipilimumab and chemotherapy at about 3 months.

Patients receiving the combination exhibited a 79% reduction in the risk for disease progression or death at 2 years (72% vs 14%; hazard ratio, 0.21; P < .0001). The median PFS was not reached with the combination vs 5.9 months with chemotherapy. The PFS benefit of nivolumab/ipilimumab held across various subgroups, including patients with KRAS or NRAS mutations and baseline lung, liver, or peritoneal metastases.

The incidence of grade 3/4 treatment-related adverse events was 23% with nivolumab/ipilimumab vs 48% in the chemotherapy arm. The most common grade 3/4 events with nivolumab/ipilimumab were diarrhea/colitis (5%), adrenal insufficiency (4%), hepatitis (3%), and inflammation of the pituitary gland (3%).

Two treatment-related deaths occurred in the combination arm — one from pneumonitis and the second from myocarditis — and none occurred in the chemotherapy arm.

Mark A. Lewis, MD, a gastrointestinal oncologist at Intermountain Healthcare in Murray, Utah, was impressed with the CHECKMATE-8HW findings. The data are shaping up to make nivolumab/ipilimumab “the next great step in metastatic CRC management beyond KEYNOTE-177,” Dr. Lewis said.

Dr. Lewis noted that the new trial makes it “imperative” to standardize testing for immunotherapy candidacy upfront. “It is completely unacceptable for any patient with metastatic CRC to not have their MMR/MSI status assessed,” he said. “Much as no oncologist would dare treat breast cancer without testing ER, PR, HER2 status, biomarkers cannot be a later-line afterthought in stage IV CRC.”

Drugmaker Bristol-Myers Squibb told this news organization that the company will be seeking a first-line indication for the combination, and anticipates approval early next year or possibly sooner, if the FDA grants a priority review.

The work was funded by Bristol-Myers Squibb and the ONO Pharmaceutical Company. Dr. Andre had numerous industry ties, including being a consultant for both BMS and Merck. He also reported honoraria from both companies. Dr. Newman and Dr. Lewis didn’t have any disclosures.

A version of this article appeared on Medscape.com.

SAN FRANCISCO — The immunotherapy combination nivolumab plus ipilimumab rivals chemotherapy as well as pembrolizumab monotherapy in the first-line treatment of metastatic colorectal cancer (CRC), new data indicated.

Findings from the CHECKMATE-8HW trial revealed that first-line nivolumab plus ipilimumab led to a significant improvement in progression-free survival (PFS) compared with chemotherapy among patients with metastatic CRC.

More specifically, at 2 years, PFS was 72% among patients with microsatellite instability–high (MSI-H) or deficient mismatch repair (dMMR) randomized to the immunotherapy combination compared with just 14% among those randomized to chemotherapy with or without targeted therapy.

The magnitude of the benefit was unexpected, especially considering patients received only four cycles of the immunotherapy combination in the trial. “It’s a good surprise,” said lead investigator Thierry Andre, MD, who presented the findings at the 2024 ASCO Gastrointestinal Cancers Symposium.

The findings indicate that nivolumab plus ipilimumab should really be “a new standard,” said Andre, a medical oncologist at Sorbonne University, Paris.

The combination as well as nivolumab alone has received US Food and Drug Administration’s (FDA’s) approval to treat MSI-H or dMMR metastatic CRC in the second line, following chemotherapy failure.

The FDA also approved pembrolizumab as first-line monotherapy for this CRC indication in 2020. The KEYNOTE-177 trial, which led to the pembrolizumab approval, reported a 2-year PFS of 48% among patients receiving the monotherapy. Andre was the lead investigator on KEYNOTE-177.

To compare PFS results for pembrolizumab and nivolumab alone, the CHECKMATE-8HW trial included a nivolumab monotherapy arm, but these results are pending, as are the overall survival findings, Andre said.

Overall, CHECKMATE-8HW must be taken into context with KEYNOTE-177, and “we need a little bit more trial data” for oncologists to decide between the two options, said Neil Newman, MD, a radiation oncologist at the University of Texas Health Science Center, San Antonio, Texas, who co-moderated Dr. Andre’s presentation.

Andre noted, however, that if the nivolumab and pembrolizumab monotherapy results are similar, most patients will likely receive the nivolumab/ipilimumab combination, given the improved PFS outcomes.

In CHECKMATE-8HW, patients were randomized to three regimens. The 202 patients in the combination arm received nivolumab 240 mg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks. The 101 patients in the chemotherapy group received investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab. And the nivolumab monotherapy arm received nivolumab 240 mg every 2 weeks for six doses, followed by nivolumab 480 mg every 4 weeks.

Treatment continued until disease progression or unacceptable toxicity over a maximum of 2 years. The median duration of treatment was 13.5 months in the nivolumab/ipilimumab arm vs 4 months in the chemotherapy arm.

PFS curves started to separate between nivolumab/ipilimumab and chemotherapy at about 3 months.

Patients receiving the combination exhibited a 79% reduction in the risk for disease progression or death at 2 years (72% vs 14%; hazard ratio, 0.21; P < .0001). The median PFS was not reached with the combination vs 5.9 months with chemotherapy. The PFS benefit of nivolumab/ipilimumab held across various subgroups, including patients with KRAS or NRAS mutations and baseline lung, liver, or peritoneal metastases.

The incidence of grade 3/4 treatment-related adverse events was 23% with nivolumab/ipilimumab vs 48% in the chemotherapy arm. The most common grade 3/4 events with nivolumab/ipilimumab were diarrhea/colitis (5%), adrenal insufficiency (4%), hepatitis (3%), and inflammation of the pituitary gland (3%).

Two treatment-related deaths occurred in the combination arm — one from pneumonitis and the second from myocarditis — and none occurred in the chemotherapy arm.

Mark A. Lewis, MD, a gastrointestinal oncologist at Intermountain Healthcare in Murray, Utah, was impressed with the CHECKMATE-8HW findings. The data are shaping up to make nivolumab/ipilimumab “the next great step in metastatic CRC management beyond KEYNOTE-177,” Dr. Lewis said.

Dr. Lewis noted that the new trial makes it “imperative” to standardize testing for immunotherapy candidacy upfront. “It is completely unacceptable for any patient with metastatic CRC to not have their MMR/MSI status assessed,” he said. “Much as no oncologist would dare treat breast cancer without testing ER, PR, HER2 status, biomarkers cannot be a later-line afterthought in stage IV CRC.”

Drugmaker Bristol-Myers Squibb told this news organization that the company will be seeking a first-line indication for the combination, and anticipates approval early next year or possibly sooner, if the FDA grants a priority review.

The work was funded by Bristol-Myers Squibb and the ONO Pharmaceutical Company. Dr. Andre had numerous industry ties, including being a consultant for both BMS and Merck. He also reported honoraria from both companies. Dr. Newman and Dr. Lewis didn’t have any disclosures.

A version of this article appeared on Medscape.com.

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Advantage of Abemaciclib Plus Endocrine Therapy for Early Breast Cancer Endures at 5 Years

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A combination of adjuvant abemaciclib and endocrine therapy significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–), node-positive early breast cancer, in updated results of a trial.

This was based on data collected over a median follow-up of 54 months. Previously reported data from this phase III study, known as monarchE, showed the same outcomes but over a 2-year treatment period, the researchers said.

Risk of cancer recurrence may be as much as 30% at 5 years in these high-risk patients, who will likely need more intense treatment, wrote Priya Rastogi, MD, of the University of Pittsburgh Medical Center, and colleagues.

In the new study published in the Journal of Clinical Oncology (2023 Jan 9. doi: 10.1200/JCO.23.019), the researchers reported 5-year efficacy results from an interim analysis of overall survival in the monarchE trial.

The intent-to-treat population included 2808 individuals randomized to abemaciclib plus ET and 2814 to ET alone; the median age was 51 years, and approximately 70% of the participants were White.

The addition of abemaciclib significantly reduced the risk of IDFS and DRFS over a median follow-up period of 54 months with hazard ratios of 0.680 and 0.675, respectively. Adjuvant abemaciclib also significantly improved DRFS over ET alone (HR 0.675).

The findings were limited by the lack of statistical significance for overall survival with abemaciclib. However, the increased benefits for IDFS and DRFS with abemaciclib plus ET vs. ET alone were consistent across all subgroups, and the benefit of abemaciclib was consistent regardless of the number of nodes involved, the researchers wrote.

“Prior reports from this trial with shorter follow-up demonstrated benefit of abemaciclib. However, with longer follow-up of a median 54 months, we see that the benefit of the drug is not only sustained (32% reduction in the risk of a disease event), but that there is further separation of the curves with an absolute difference in IDFS and DRFS rates of 7.6% and 6.7, comparing the ET alone vs. ET plus abemaciclib arms,” study coauthor Matthew P. Goetz, MD, said in an interview.

Although statistical significance was not reached for overall survival, fewer deaths occurred in the abemaciclib-plus-ET group compared with the ET-only group, said Dr. Goetz, of the Mayo Clinic, Rochester, Minnesota. However, patients with the worst prognosis (Ki-67–high subgroup) tended to have higher overall survival.

A total of 208 deaths occurred in the combination group vs. 234 in the ET-only group, and no new safety signals were observed. The occurrence of serious adverse events of any cause was similar in the abemaciclib group and the ET-only group (6.5% vs. 7.3%).

“These data are a pleasant surprise, as there were concerns that the benefit of the drug seen with shorter follow-up would wane over time,” Dr. Goetz said. “However, the opposite has occurred; with increasing length of follow-up, the curves continue to separate.”

Based on the new results, “we have high confidence that for patients with ER+/HER2- breast cancer at high risk of recurrence, the addition of 2 years of adjuvant abemaciclib to ET results in clinically significant improvements in IDFS,” he said.

Looking ahead, “we need additional follow-up to determine whether the benefit we now see in terms of IDFS will eventually translate into improvements in overall survival,” Dr. Goetz said. “We need to identify biomarkers that can identify patients at risk for early recurrence despite administration of adjuvant abemaciclib and further, biomarkers that will allow us to select patients that can be safely treated with ET alone.”

 

 

 

Findings Confirm Value of Combined Treatment

“It was reassuring to see the continued benefit at 5 years with adjuvant abemaciclib in combination with endocrine therapy compared to endocrine therapy alone in this high-risk HR+, HER2– EBC [early breast cancer] population,” Manali Ajay Bhave, MD, a medical oncologist at Emory University, Atlanta, said in an interview.

“While the interim overall survival analysis was not significant, further follow-up is necessary to truly discern a survival benefit particularly in this patient population where a survival advantage may not be seen for several years,” she added.

The current study supports the continued use of adjuvant abemaciclib in high-risk HR+, HER2– EBC patients, Dr. Bhave said. “Investigation of novel endocrine agents in the adjuvant setting for patients with high risk, HR+ HER2– EBC is needed to further improve outcomes.”
 

Urgent Need to Improve Adjuvant Therapy

“The monarchE study is a timely study aimed at improving adjuvant treatments in ER+ breast cancer to reduce risk of late recurrences,” Malinda T. West, MD, of the University of Wisconsin, said in an interview. “Late recurrences occurring decades later is a risk associated with ER+ breast cancer, and the risk of breast cancer recurrence is highest in those with larger tumors and nodal involvement.

“Abemaciclib is one of the three FDA-approved cyclin-dependent kinase 4/6 inhibitors in metastatic ER+ breast cancer based on demonstrated efficacy and safety in the metastatic setting compared to endocrine therapy alone, which was the rationale for expanded use of abemaciclib into the adjuvant setting for those at high risk for recurrence and basis of the monarchE trial,” said Dr. West.

An important criterion for inclusion was the randomization to abemaciclib required within 16 months of definitive breast cancer surgery, which reflected a window of time in which to start adjuvant abemaciclib, Dr. West said. “Exclusion criteria were those with a history of thromboembolic events, as abemaciclib carries a warning for venous thromboembolism,” she added.

In the monarchE follow-up, Dr. West said she was encouraged by the persistent and widening benefit with 2 years of added abemaciclib to endocrine therapy in reducing IDFS and DRFS compared to endocrine therapy alone.

Dr. West advised clinicians to consider initiating the therapy for up to 16 months after definitive breast surgery, because doing so may allow for recovery from surgery, chemotherapy, and radiation.

The findings tell physicians to “use caution with adding abemaciclib in those with a history of thromboembolic events or VTE risk factors as abemaciclib has a known VTE warning and this population was excluded in the monarchE trial,” she noted.

“Continued long-term follow up of those in this study will be important to determine survival benefits and how the predictive biomarker Ki-67 may impact survival outcomes,” she said.

The study was supported by Eli Lilly. Lead author Dr. Rastogi disclosed travel, accommodations, and expenses from Genentech/Roche, Lilly, and AstraZeneca. Several coauthors disclosed stock or ownership interests and/or other relationships with Lilly and other pharmaceutical companies. Dr. Goetz receives research funding from the National Institutes of Health. Dr. Bhave and Dr. West had no financial conflicts to disclose.

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A combination of adjuvant abemaciclib and endocrine therapy significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–), node-positive early breast cancer, in updated results of a trial.

This was based on data collected over a median follow-up of 54 months. Previously reported data from this phase III study, known as monarchE, showed the same outcomes but over a 2-year treatment period, the researchers said.

Risk of cancer recurrence may be as much as 30% at 5 years in these high-risk patients, who will likely need more intense treatment, wrote Priya Rastogi, MD, of the University of Pittsburgh Medical Center, and colleagues.

In the new study published in the Journal of Clinical Oncology (2023 Jan 9. doi: 10.1200/JCO.23.019), the researchers reported 5-year efficacy results from an interim analysis of overall survival in the monarchE trial.

The intent-to-treat population included 2808 individuals randomized to abemaciclib plus ET and 2814 to ET alone; the median age was 51 years, and approximately 70% of the participants were White.

The addition of abemaciclib significantly reduced the risk of IDFS and DRFS over a median follow-up period of 54 months with hazard ratios of 0.680 and 0.675, respectively. Adjuvant abemaciclib also significantly improved DRFS over ET alone (HR 0.675).

The findings were limited by the lack of statistical significance for overall survival with abemaciclib. However, the increased benefits for IDFS and DRFS with abemaciclib plus ET vs. ET alone were consistent across all subgroups, and the benefit of abemaciclib was consistent regardless of the number of nodes involved, the researchers wrote.

“Prior reports from this trial with shorter follow-up demonstrated benefit of abemaciclib. However, with longer follow-up of a median 54 months, we see that the benefit of the drug is not only sustained (32% reduction in the risk of a disease event), but that there is further separation of the curves with an absolute difference in IDFS and DRFS rates of 7.6% and 6.7, comparing the ET alone vs. ET plus abemaciclib arms,” study coauthor Matthew P. Goetz, MD, said in an interview.

Although statistical significance was not reached for overall survival, fewer deaths occurred in the abemaciclib-plus-ET group compared with the ET-only group, said Dr. Goetz, of the Mayo Clinic, Rochester, Minnesota. However, patients with the worst prognosis (Ki-67–high subgroup) tended to have higher overall survival.

A total of 208 deaths occurred in the combination group vs. 234 in the ET-only group, and no new safety signals were observed. The occurrence of serious adverse events of any cause was similar in the abemaciclib group and the ET-only group (6.5% vs. 7.3%).

“These data are a pleasant surprise, as there were concerns that the benefit of the drug seen with shorter follow-up would wane over time,” Dr. Goetz said. “However, the opposite has occurred; with increasing length of follow-up, the curves continue to separate.”

Based on the new results, “we have high confidence that for patients with ER+/HER2- breast cancer at high risk of recurrence, the addition of 2 years of adjuvant abemaciclib to ET results in clinically significant improvements in IDFS,” he said.

Looking ahead, “we need additional follow-up to determine whether the benefit we now see in terms of IDFS will eventually translate into improvements in overall survival,” Dr. Goetz said. “We need to identify biomarkers that can identify patients at risk for early recurrence despite administration of adjuvant abemaciclib and further, biomarkers that will allow us to select patients that can be safely treated with ET alone.”

 

 

 

Findings Confirm Value of Combined Treatment

“It was reassuring to see the continued benefit at 5 years with adjuvant abemaciclib in combination with endocrine therapy compared to endocrine therapy alone in this high-risk HR+, HER2– EBC [early breast cancer] population,” Manali Ajay Bhave, MD, a medical oncologist at Emory University, Atlanta, said in an interview.

“While the interim overall survival analysis was not significant, further follow-up is necessary to truly discern a survival benefit particularly in this patient population where a survival advantage may not be seen for several years,” she added.

The current study supports the continued use of adjuvant abemaciclib in high-risk HR+, HER2– EBC patients, Dr. Bhave said. “Investigation of novel endocrine agents in the adjuvant setting for patients with high risk, HR+ HER2– EBC is needed to further improve outcomes.”
 

Urgent Need to Improve Adjuvant Therapy

“The monarchE study is a timely study aimed at improving adjuvant treatments in ER+ breast cancer to reduce risk of late recurrences,” Malinda T. West, MD, of the University of Wisconsin, said in an interview. “Late recurrences occurring decades later is a risk associated with ER+ breast cancer, and the risk of breast cancer recurrence is highest in those with larger tumors and nodal involvement.

“Abemaciclib is one of the three FDA-approved cyclin-dependent kinase 4/6 inhibitors in metastatic ER+ breast cancer based on demonstrated efficacy and safety in the metastatic setting compared to endocrine therapy alone, which was the rationale for expanded use of abemaciclib into the adjuvant setting for those at high risk for recurrence and basis of the monarchE trial,” said Dr. West.

An important criterion for inclusion was the randomization to abemaciclib required within 16 months of definitive breast cancer surgery, which reflected a window of time in which to start adjuvant abemaciclib, Dr. West said. “Exclusion criteria were those with a history of thromboembolic events, as abemaciclib carries a warning for venous thromboembolism,” she added.

In the monarchE follow-up, Dr. West said she was encouraged by the persistent and widening benefit with 2 years of added abemaciclib to endocrine therapy in reducing IDFS and DRFS compared to endocrine therapy alone.

Dr. West advised clinicians to consider initiating the therapy for up to 16 months after definitive breast surgery, because doing so may allow for recovery from surgery, chemotherapy, and radiation.

The findings tell physicians to “use caution with adding abemaciclib in those with a history of thromboembolic events or VTE risk factors as abemaciclib has a known VTE warning and this population was excluded in the monarchE trial,” she noted.

“Continued long-term follow up of those in this study will be important to determine survival benefits and how the predictive biomarker Ki-67 may impact survival outcomes,” she said.

The study was supported by Eli Lilly. Lead author Dr. Rastogi disclosed travel, accommodations, and expenses from Genentech/Roche, Lilly, and AstraZeneca. Several coauthors disclosed stock or ownership interests and/or other relationships with Lilly and other pharmaceutical companies. Dr. Goetz receives research funding from the National Institutes of Health. Dr. Bhave and Dr. West had no financial conflicts to disclose.

A combination of adjuvant abemaciclib and endocrine therapy significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–), node-positive early breast cancer, in updated results of a trial.

This was based on data collected over a median follow-up of 54 months. Previously reported data from this phase III study, known as monarchE, showed the same outcomes but over a 2-year treatment period, the researchers said.

Risk of cancer recurrence may be as much as 30% at 5 years in these high-risk patients, who will likely need more intense treatment, wrote Priya Rastogi, MD, of the University of Pittsburgh Medical Center, and colleagues.

In the new study published in the Journal of Clinical Oncology (2023 Jan 9. doi: 10.1200/JCO.23.019), the researchers reported 5-year efficacy results from an interim analysis of overall survival in the monarchE trial.

The intent-to-treat population included 2808 individuals randomized to abemaciclib plus ET and 2814 to ET alone; the median age was 51 years, and approximately 70% of the participants were White.

The addition of abemaciclib significantly reduced the risk of IDFS and DRFS over a median follow-up period of 54 months with hazard ratios of 0.680 and 0.675, respectively. Adjuvant abemaciclib also significantly improved DRFS over ET alone (HR 0.675).

The findings were limited by the lack of statistical significance for overall survival with abemaciclib. However, the increased benefits for IDFS and DRFS with abemaciclib plus ET vs. ET alone were consistent across all subgroups, and the benefit of abemaciclib was consistent regardless of the number of nodes involved, the researchers wrote.

“Prior reports from this trial with shorter follow-up demonstrated benefit of abemaciclib. However, with longer follow-up of a median 54 months, we see that the benefit of the drug is not only sustained (32% reduction in the risk of a disease event), but that there is further separation of the curves with an absolute difference in IDFS and DRFS rates of 7.6% and 6.7, comparing the ET alone vs. ET plus abemaciclib arms,” study coauthor Matthew P. Goetz, MD, said in an interview.

Although statistical significance was not reached for overall survival, fewer deaths occurred in the abemaciclib-plus-ET group compared with the ET-only group, said Dr. Goetz, of the Mayo Clinic, Rochester, Minnesota. However, patients with the worst prognosis (Ki-67–high subgroup) tended to have higher overall survival.

A total of 208 deaths occurred in the combination group vs. 234 in the ET-only group, and no new safety signals were observed. The occurrence of serious adverse events of any cause was similar in the abemaciclib group and the ET-only group (6.5% vs. 7.3%).

“These data are a pleasant surprise, as there were concerns that the benefit of the drug seen with shorter follow-up would wane over time,” Dr. Goetz said. “However, the opposite has occurred; with increasing length of follow-up, the curves continue to separate.”

Based on the new results, “we have high confidence that for patients with ER+/HER2- breast cancer at high risk of recurrence, the addition of 2 years of adjuvant abemaciclib to ET results in clinically significant improvements in IDFS,” he said.

Looking ahead, “we need additional follow-up to determine whether the benefit we now see in terms of IDFS will eventually translate into improvements in overall survival,” Dr. Goetz said. “We need to identify biomarkers that can identify patients at risk for early recurrence despite administration of adjuvant abemaciclib and further, biomarkers that will allow us to select patients that can be safely treated with ET alone.”

 

 

 

Findings Confirm Value of Combined Treatment

“It was reassuring to see the continued benefit at 5 years with adjuvant abemaciclib in combination with endocrine therapy compared to endocrine therapy alone in this high-risk HR+, HER2– EBC [early breast cancer] population,” Manali Ajay Bhave, MD, a medical oncologist at Emory University, Atlanta, said in an interview.

“While the interim overall survival analysis was not significant, further follow-up is necessary to truly discern a survival benefit particularly in this patient population where a survival advantage may not be seen for several years,” she added.

The current study supports the continued use of adjuvant abemaciclib in high-risk HR+, HER2– EBC patients, Dr. Bhave said. “Investigation of novel endocrine agents in the adjuvant setting for patients with high risk, HR+ HER2– EBC is needed to further improve outcomes.”
 

Urgent Need to Improve Adjuvant Therapy

“The monarchE study is a timely study aimed at improving adjuvant treatments in ER+ breast cancer to reduce risk of late recurrences,” Malinda T. West, MD, of the University of Wisconsin, said in an interview. “Late recurrences occurring decades later is a risk associated with ER+ breast cancer, and the risk of breast cancer recurrence is highest in those with larger tumors and nodal involvement.

“Abemaciclib is one of the three FDA-approved cyclin-dependent kinase 4/6 inhibitors in metastatic ER+ breast cancer based on demonstrated efficacy and safety in the metastatic setting compared to endocrine therapy alone, which was the rationale for expanded use of abemaciclib into the adjuvant setting for those at high risk for recurrence and basis of the monarchE trial,” said Dr. West.

An important criterion for inclusion was the randomization to abemaciclib required within 16 months of definitive breast cancer surgery, which reflected a window of time in which to start adjuvant abemaciclib, Dr. West said. “Exclusion criteria were those with a history of thromboembolic events, as abemaciclib carries a warning for venous thromboembolism,” she added.

In the monarchE follow-up, Dr. West said she was encouraged by the persistent and widening benefit with 2 years of added abemaciclib to endocrine therapy in reducing IDFS and DRFS compared to endocrine therapy alone.

Dr. West advised clinicians to consider initiating the therapy for up to 16 months after definitive breast surgery, because doing so may allow for recovery from surgery, chemotherapy, and radiation.

The findings tell physicians to “use caution with adding abemaciclib in those with a history of thromboembolic events or VTE risk factors as abemaciclib has a known VTE warning and this population was excluded in the monarchE trial,” she noted.

“Continued long-term follow up of those in this study will be important to determine survival benefits and how the predictive biomarker Ki-67 may impact survival outcomes,” she said.

The study was supported by Eli Lilly. Lead author Dr. Rastogi disclosed travel, accommodations, and expenses from Genentech/Roche, Lilly, and AstraZeneca. Several coauthors disclosed stock or ownership interests and/or other relationships with Lilly and other pharmaceutical companies. Dr. Goetz receives research funding from the National Institutes of Health. Dr. Bhave and Dr. West had no financial conflicts to disclose.

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FROM THE JOURNAL OF CLINICAL ONCOLOGY

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Radiation Oncologists Fight for Payment Reform Amid Cuts

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Wed, 01/24/2024 - 16:42

Radiation oncologists from the largest professional societies have come together to lobby for Medicare payment reform.

The American Society for Radiation Oncology (ASTRO) recently announced its partnership with three other groups — the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology — to change how the specialty is paid for services. 

Over the past decade, radiation oncologists have seen a 23% drop in Medicare reimbursement for radiation therapy services, with more cuts to come, according to a press release from ASTRO.

Traditionally, Medicare has reimbursed on the basis of the fraction of radiation delivered. But with moves toward hypofractionated regimens, deescalated therapy, and other changes in the field, reimbursement has continued to dwindle. 

The cuts have led to practice consolidation and closures that threaten patient access especially in rural and underserved areas, a spokesperson for the group told this news organization.

To reverse this trend, ASTRO recently proposed the Radiation Oncology Case Rate program, a legislative initiative to base reimbursements on patient volumes instead of fractions delivered. 

ASTRO is currently drafting a congressional bill to change the current payment structure, which “has become untenable,” the spokesperson said. 

A version of this article appeared on Medscape.com.

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Radiation oncologists from the largest professional societies have come together to lobby for Medicare payment reform.

The American Society for Radiation Oncology (ASTRO) recently announced its partnership with three other groups — the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology — to change how the specialty is paid for services. 

Over the past decade, radiation oncologists have seen a 23% drop in Medicare reimbursement for radiation therapy services, with more cuts to come, according to a press release from ASTRO.

Traditionally, Medicare has reimbursed on the basis of the fraction of radiation delivered. But with moves toward hypofractionated regimens, deescalated therapy, and other changes in the field, reimbursement has continued to dwindle. 

The cuts have led to practice consolidation and closures that threaten patient access especially in rural and underserved areas, a spokesperson for the group told this news organization.

To reverse this trend, ASTRO recently proposed the Radiation Oncology Case Rate program, a legislative initiative to base reimbursements on patient volumes instead of fractions delivered. 

ASTRO is currently drafting a congressional bill to change the current payment structure, which “has become untenable,” the spokesperson said. 

A version of this article appeared on Medscape.com.

Radiation oncologists from the largest professional societies have come together to lobby for Medicare payment reform.

The American Society for Radiation Oncology (ASTRO) recently announced its partnership with three other groups — the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology — to change how the specialty is paid for services. 

Over the past decade, radiation oncologists have seen a 23% drop in Medicare reimbursement for radiation therapy services, with more cuts to come, according to a press release from ASTRO.

Traditionally, Medicare has reimbursed on the basis of the fraction of radiation delivered. But with moves toward hypofractionated regimens, deescalated therapy, and other changes in the field, reimbursement has continued to dwindle. 

The cuts have led to practice consolidation and closures that threaten patient access especially in rural and underserved areas, a spokesperson for the group told this news organization.

To reverse this trend, ASTRO recently proposed the Radiation Oncology Case Rate program, a legislative initiative to base reimbursements on patient volumes instead of fractions delivered. 

ASTRO is currently drafting a congressional bill to change the current payment structure, which “has become untenable,” the spokesperson said. 

A version of this article appeared on Medscape.com.

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Standard Therapy Beats Out Primary Surgery in Rectal Cancer

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Tue, 01/23/2024 - 00:25

 

TOPLINE:

Patients with locally advanced rectal cancer fare better with standard preoperative chemoradiation followed by surgery than with primary surgery and adjuvant chemoradiation, demonstrating better disease-free survival and lower recurrence rates.

METHODOLOGY:

  • The standard treatment of locally advanced rectal cancer is chemoradiation followed by surgery, which is known to reduce the likelihood of local recurrence; however, it is also linked to adverse effects including  and bowel/sexual dysfunction.
  • A previous trial found that preoperative MRI could delineate tumor involvement of the mesorectal fascia (MRF).
  • This Chinese, noninferiority trial tested whether patients with locally advanced rectal cancer with MRI-predicted negative MRF can skip preoperative chemoradiation.
  • The study included 275 patients with T3-4aN0 or T1-4aN1-2 rectal adenocarcinoma, an inferior tumor edge 6-12 cm from the anal verge, and gross primary or nodal disease > 1 mm from the MRF — all based on preoperative MRI.
  • Patients in the intervention group, 140, were assigned to neoadjuvant chemoradiation (50.4 Gy in 28 fractions with  followed by capecitabine/ started 4 weeks after surgery) and the remaining 135 to upfront surgery followed by adjuvant chemo/chemoradiation when there was tumor within 1 mm of circumferential margins.

TAKEAWAY:

  • After a median follow-up of 34.6 months, there were six (4.4%) local recurrences in the intervention group and none in the control group.
  • In the intention-to-treat population, the 3-year disease-free survival rate was 81.8% in the intervention group vs 85.4% in the control group (hazard ratio [HR], 1.76).
  • In the per protocol dataset, the 3-year disease-free survival rate was 81.1% in the primary surgery group vs 86.6% in the preoperative chemoradiation group — a difference of −5.4% (HR, 2.02), prompting the researchers to stop the trial early.

IN PRACTICE:

“This trial was shut down earlier due to an excessive number of [disease-free survival] and local recurrence events observed in the interventional group of primary surgery. Based on our findings, in [locally advanced rectal cancer] patients with high risk though negative MRF, primary surgery would potentially compromise their [disease-free survival] rates. Therefore, primary surgery is an inferior strategy, compared to preoperative [chemoradiation] followed by surgery, and cannot be recommended for [locally advanced rectal cancer] patients in clinical practice,” the authors concluded.

SOURCE:

The study, with first author Jun Li, MD, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, was published online in the International Journal of Radiation Oncology, Biology, Physics.

LIMITATIONS:

The limited sample size will result in compromises in stratified randomization and lower the power for survival analysis. A relatively high proportion of patients (n = 32) crossed over from the neoadjuvant (chemoradiation) group to the primary surgery group. Follow-up time was relatively short, with only 43% of patients completing 3 years of follow-up.

DISCLOSURES:

The study received no commercial funding. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

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TOPLINE:

Patients with locally advanced rectal cancer fare better with standard preoperative chemoradiation followed by surgery than with primary surgery and adjuvant chemoradiation, demonstrating better disease-free survival and lower recurrence rates.

METHODOLOGY:

  • The standard treatment of locally advanced rectal cancer is chemoradiation followed by surgery, which is known to reduce the likelihood of local recurrence; however, it is also linked to adverse effects including  and bowel/sexual dysfunction.
  • A previous trial found that preoperative MRI could delineate tumor involvement of the mesorectal fascia (MRF).
  • This Chinese, noninferiority trial tested whether patients with locally advanced rectal cancer with MRI-predicted negative MRF can skip preoperative chemoradiation.
  • The study included 275 patients with T3-4aN0 or T1-4aN1-2 rectal adenocarcinoma, an inferior tumor edge 6-12 cm from the anal verge, and gross primary or nodal disease > 1 mm from the MRF — all based on preoperative MRI.
  • Patients in the intervention group, 140, were assigned to neoadjuvant chemoradiation (50.4 Gy in 28 fractions with  followed by capecitabine/ started 4 weeks after surgery) and the remaining 135 to upfront surgery followed by adjuvant chemo/chemoradiation when there was tumor within 1 mm of circumferential margins.

TAKEAWAY:

  • After a median follow-up of 34.6 months, there were six (4.4%) local recurrences in the intervention group and none in the control group.
  • In the intention-to-treat population, the 3-year disease-free survival rate was 81.8% in the intervention group vs 85.4% in the control group (hazard ratio [HR], 1.76).
  • In the per protocol dataset, the 3-year disease-free survival rate was 81.1% in the primary surgery group vs 86.6% in the preoperative chemoradiation group — a difference of −5.4% (HR, 2.02), prompting the researchers to stop the trial early.

IN PRACTICE:

“This trial was shut down earlier due to an excessive number of [disease-free survival] and local recurrence events observed in the interventional group of primary surgery. Based on our findings, in [locally advanced rectal cancer] patients with high risk though negative MRF, primary surgery would potentially compromise their [disease-free survival] rates. Therefore, primary surgery is an inferior strategy, compared to preoperative [chemoradiation] followed by surgery, and cannot be recommended for [locally advanced rectal cancer] patients in clinical practice,” the authors concluded.

SOURCE:

The study, with first author Jun Li, MD, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, was published online in the International Journal of Radiation Oncology, Biology, Physics.

LIMITATIONS:

The limited sample size will result in compromises in stratified randomization and lower the power for survival analysis. A relatively high proportion of patients (n = 32) crossed over from the neoadjuvant (chemoradiation) group to the primary surgery group. Follow-up time was relatively short, with only 43% of patients completing 3 years of follow-up.

DISCLOSURES:

The study received no commercial funding. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

 

TOPLINE:

Patients with locally advanced rectal cancer fare better with standard preoperative chemoradiation followed by surgery than with primary surgery and adjuvant chemoradiation, demonstrating better disease-free survival and lower recurrence rates.

METHODOLOGY:

  • The standard treatment of locally advanced rectal cancer is chemoradiation followed by surgery, which is known to reduce the likelihood of local recurrence; however, it is also linked to adverse effects including  and bowel/sexual dysfunction.
  • A previous trial found that preoperative MRI could delineate tumor involvement of the mesorectal fascia (MRF).
  • This Chinese, noninferiority trial tested whether patients with locally advanced rectal cancer with MRI-predicted negative MRF can skip preoperative chemoradiation.
  • The study included 275 patients with T3-4aN0 or T1-4aN1-2 rectal adenocarcinoma, an inferior tumor edge 6-12 cm from the anal verge, and gross primary or nodal disease > 1 mm from the MRF — all based on preoperative MRI.
  • Patients in the intervention group, 140, were assigned to neoadjuvant chemoradiation (50.4 Gy in 28 fractions with  followed by capecitabine/ started 4 weeks after surgery) and the remaining 135 to upfront surgery followed by adjuvant chemo/chemoradiation when there was tumor within 1 mm of circumferential margins.

TAKEAWAY:

  • After a median follow-up of 34.6 months, there were six (4.4%) local recurrences in the intervention group and none in the control group.
  • In the intention-to-treat population, the 3-year disease-free survival rate was 81.8% in the intervention group vs 85.4% in the control group (hazard ratio [HR], 1.76).
  • In the per protocol dataset, the 3-year disease-free survival rate was 81.1% in the primary surgery group vs 86.6% in the preoperative chemoradiation group — a difference of −5.4% (HR, 2.02), prompting the researchers to stop the trial early.

IN PRACTICE:

“This trial was shut down earlier due to an excessive number of [disease-free survival] and local recurrence events observed in the interventional group of primary surgery. Based on our findings, in [locally advanced rectal cancer] patients with high risk though negative MRF, primary surgery would potentially compromise their [disease-free survival] rates. Therefore, primary surgery is an inferior strategy, compared to preoperative [chemoradiation] followed by surgery, and cannot be recommended for [locally advanced rectal cancer] patients in clinical practice,” the authors concluded.

SOURCE:

The study, with first author Jun Li, MD, Department of Colorectal Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China, was published online in the International Journal of Radiation Oncology, Biology, Physics.

LIMITATIONS:

The limited sample size will result in compromises in stratified randomization and lower the power for survival analysis. A relatively high proportion of patients (n = 32) crossed over from the neoadjuvant (chemoradiation) group to the primary surgery group. Follow-up time was relatively short, with only 43% of patients completing 3 years of follow-up.

DISCLOSURES:

The study received no commercial funding. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

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Oncologists Sound the Alarm About Rise of White Bagging

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Tue, 01/30/2024 - 16:11

For years, oncologist John DiPersio, MD, PhD, had faced frustrating encounters with insurers that only cover medications through a process called white bagging.

Instead of the traditional buy-and-bill pathway where oncologists purchase specialty drugs, such as infusion medications, directly from the distributor or manufacturer, white bagging requires physicians to receive these drugs from a specialty pharmacy.

On its face, the differences may seem minor. However, as Dr. DiPersio knows well, the consequences for oncologists and patients are not.

White bagging, research showed, leads to higher costs for patients and lower reimbursement for oncology practices. The practice can also create safety issues for patients.

That is why Dr. DiPersio’s cancer center does not allow white bagging.

And when insurers refuse to reconsider the white bagging policy, his cancer team is left with few options.

“Sometimes, we have to redirect patients to other places,” said Dr. DiPersio, a bone marrow transplant specialist at Siteman Cancer Center, Washington University, St. Louis.

In emergency instances where patients cannot wait, Dr. DiPersio’s team will administer their own stock of a drug. In such cases, “we accept the fact that by not allowing white bagging, there may be nonpayment. We take the hit as far as cost.”

Increasingly, white bagging mandates are becoming harder for practices to avoid.

In a 2021 survey, 87% of Association of Community Cancer Centers members said white bagging has become an insurer mandate for some of their patients.

2023 analysis from Adam J. Fein, PhD, of Drug Channels Institute, Philadelphia, found that white bagging accounted for 17% of infused oncology product sourcing from clinics and 38% from hospital outpatient departments, up from 15% to 28% in 2019. Another practice called brown bagging, where specialty pharmacies send drugs directly to patients, creates many of the same issues but is much less prevalent than white bagging.

This change reflects “the broader battle over oncology margins” and insurers’ “attempts to shift costs to providers, patients, and manufacturers,” Dr. Fein wrote in his 2023 report.
 

White Bagging: Who Benefits?

At its core, white bagging changes how drugs are covered and reimbursed. Under buy and bill, drugs fall under a patient’s medical benefit. Oncologists purchase drugs directly from the manufacturer or distributor and receive reimbursement from the insurance company for both the cost of the drug as well as for administering it to patients.

Under white bagging, drugs fall under a patient’s pharmacy benefit. In these instances, a specialty pharmacy prepares the infusion ahead of time and ships it directly to the physician’s office or clinic. Because oncologists do not purchase the drug directly, they cannot bill insurers for it; instead, the pharmacy receives reimbursement for the drug and the provider is reimbursed for administering it.

Insurance companies argue that white bagging reduces patients’ out-of-pocket costs “by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” according to advocacy group America’s Health Insurance Plans (AHIP).

Data from AHIP suggested that hospitals mark up the price of cancer drugs considerably, charging about twice as much as a specialty pharmacy, and that physician’s offices also charge about 23% more. However, these figures highlight how much insurers are billed, not necessarily how much patients ultimately pay.

Other evidence shows that white bagging raises costs for patients while reducing reimbursement for oncologists and saving insurance companies money.

A recent analysis in JAMA Network Open, which looked at 50 cancer drugs associated with the highest total spending from the 2020 Medicare Part B, found that mean insurance payments to providers were more than $2000 lower for drugs distributed under bagging than traditional buy and bill: $7405 vs $9547 per patient per month. Investigators found the same pattern in median insurance payments: $5746 vs $6681. Patients also paid more out-of-pocket each month with bagging vs buy and bill: $315 vs $145.

For patients with private insurance, “out-of-pocket costs were higher under bagging practice than the traditional buy-and-bill practice,” said lead author Ya-Chen Tina Shih, PhD, a professor in the department of radiation oncology at UCLA Health, Los Angeles.

White bagging is entirely for the profit of health insurers, specialty pharmacies, and pharmacy benefit managers, the middlemen who negotiate drug prices on behalf of payers.

Many people may not realize the underlying money-making strategies behind white bagging, explained Ted Okon, executive director for Community Oncology Alliance, which opposes the practice. Often, an insurer, pharmacy benefit manager, and mail order pharmacy involved in the process are all affiliated with the same corporation. In such cases, an insurer has a financial motive to control the source of medications and steer business to its affiliated pharmacies, Mr. Okon said.

When a single corporation owns numerous parts of the drug supply chain, insurers end up having “sway over what drug to use and then how the patient is going to get it,” Mr. Okon said. If the specialty pharmacy is a 340B contract pharmacy, it likely also receives a sizable discount on the drug and can make more money through white bagging.
 

 

 

Dangerous to Patients?

On the safety front, proponents of white bagging say the process is safe and efficient.

Specialty pharmacies are used only for prescription drugs that can be safely delivered, said AHIP spokesman David Allen.

In addition to having the same supply chain safety requirements as any other dispensing pharmacy, “specialty pharmacies also must meet additional safety requirements for specialty drugs” to ensure “the safe storage, handling, and dispensing of the drugs,” Mr. Allen explained.

However, oncologists argue that white bagging can be dangerous.

With white bagging, specialty pharmacies send a specified dose to practices, which does not allow practices to source and mix the drug themselves or make essential last-minute dose-related changes — something that happens every day in the clinic, said Debra Patt, MD, PhD, MBA, executive vice president for policy and strategy for Texas Oncology, Dallas.

White bagging also increases the risk for drug contamination, results in drug waste if the medication can’t be used, and can create delays in care.

Essentially, white bagging takes control away from oncologists and makes patient care more unpredictable and complex, explained Dr. Patt, president of the Texas Society of Clinical Oncology, Rockville, Maryland.

Dr. Patt, who does not allow white bagging in her practice, recalled a recent patient with metastatic breast cancer who came to the clinic for trastuzumab deruxtecan. The patient had been experiencing acute abdominal pain. After an exam and CT, Dr. Patt found the breast cancer had grown and moved into the patient’s liver.

“I had to discontinue that plan and change to a different chemotherapy,” she said. “If we had white bagged, that would have been a waste of several thousand dollars. Also, the patient would have to wait for the new medication to be white bagged, a delay that would be at least a week and the patient would have to come back at another time.”

When asked about the safety concerns associated with white bagging, Lemrey “Al” Carter, MS, PharmD, RPh, executive director of the National Association of Boards of Pharmacy (NABP), said the NABP “acknowledges that all these issues exist.

“It is unfortunate if patient care or costs are negatively impacted,” Dr. Carter said, adding that “boards of pharmacy can investigate if they are made aware of safety concerns at the pharmacy level. If a violation of the pharmacy laws or rules is found, boards can take action.”
 

More Legislation to Prevent Bagging

As white bagging mandates from insurance companies ramp up, more practices and states are banning it.

In the Association of Community Cancer Centers’ 2021 survey, 59% of members said their cancer program or practice does not allow white bagging.

At least 15 states have introduced legislation that restricts and/or prohibits white and brown bagging practices, according to a 2023 report by the Institute for Clinical and Economic Review. Some of the proposed laws would restrict mandates by stipulating that physicians are reimbursed at the contracted amount for clinician-administered drugs, whether obtained from a pharmacy or the manufacturer.

Louisiana, Vermont, and Minnesota were the first to enact anti–white bagging laws. Louisiana’s law, for example, enacted in 2021, bans white bagging and requires insurers to reimburse providers for physician-administered drugs if obtained from out-of-network pharmacies.

When the legislation passed, white bagging was just starting to enter the healthcare market in Louisiana, and the state wanted to act proactively, said Kathy W. Oubre, MS, CEO of the Pontchartrain Cancer Center, Covington, Louisiana, and president of the Coalition of Hematology and Oncology Practices, Mountain View, California.

“We recognized the growing concern around it,” Ms. Oubre said. The state legislature at the time included physicians and pharmacists who “really understood from a practice and patient perspective, the harm that policy could do.”

Ms. Oubre would like to see more legislation in other states and believes Louisiana’s law is a good model.

At the federal level, the American Hospital Association and American Society of Health-System Pharmacists have also urged the US Food and Drug Administration to take appropriate enforcement action to protect patients from white bagging.

Legislation that bars white bagging mandates is the most reasonable way to support timely and appropriate access to cancer care, Dr. Patt said. In the absence of such legislation, she said oncologists can only opt out of insurance contracts that may require the practice.

“That is a difficult position to put oncologists in,” she said.

A version of this article appeared on Medscape.com.

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For years, oncologist John DiPersio, MD, PhD, had faced frustrating encounters with insurers that only cover medications through a process called white bagging.

Instead of the traditional buy-and-bill pathway where oncologists purchase specialty drugs, such as infusion medications, directly from the distributor or manufacturer, white bagging requires physicians to receive these drugs from a specialty pharmacy.

On its face, the differences may seem minor. However, as Dr. DiPersio knows well, the consequences for oncologists and patients are not.

White bagging, research showed, leads to higher costs for patients and lower reimbursement for oncology practices. The practice can also create safety issues for patients.

That is why Dr. DiPersio’s cancer center does not allow white bagging.

And when insurers refuse to reconsider the white bagging policy, his cancer team is left with few options.

“Sometimes, we have to redirect patients to other places,” said Dr. DiPersio, a bone marrow transplant specialist at Siteman Cancer Center, Washington University, St. Louis.

In emergency instances where patients cannot wait, Dr. DiPersio’s team will administer their own stock of a drug. In such cases, “we accept the fact that by not allowing white bagging, there may be nonpayment. We take the hit as far as cost.”

Increasingly, white bagging mandates are becoming harder for practices to avoid.

In a 2021 survey, 87% of Association of Community Cancer Centers members said white bagging has become an insurer mandate for some of their patients.

2023 analysis from Adam J. Fein, PhD, of Drug Channels Institute, Philadelphia, found that white bagging accounted for 17% of infused oncology product sourcing from clinics and 38% from hospital outpatient departments, up from 15% to 28% in 2019. Another practice called brown bagging, where specialty pharmacies send drugs directly to patients, creates many of the same issues but is much less prevalent than white bagging.

This change reflects “the broader battle over oncology margins” and insurers’ “attempts to shift costs to providers, patients, and manufacturers,” Dr. Fein wrote in his 2023 report.
 

White Bagging: Who Benefits?

At its core, white bagging changes how drugs are covered and reimbursed. Under buy and bill, drugs fall under a patient’s medical benefit. Oncologists purchase drugs directly from the manufacturer or distributor and receive reimbursement from the insurance company for both the cost of the drug as well as for administering it to patients.

Under white bagging, drugs fall under a patient’s pharmacy benefit. In these instances, a specialty pharmacy prepares the infusion ahead of time and ships it directly to the physician’s office or clinic. Because oncologists do not purchase the drug directly, they cannot bill insurers for it; instead, the pharmacy receives reimbursement for the drug and the provider is reimbursed for administering it.

Insurance companies argue that white bagging reduces patients’ out-of-pocket costs “by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” according to advocacy group America’s Health Insurance Plans (AHIP).

Data from AHIP suggested that hospitals mark up the price of cancer drugs considerably, charging about twice as much as a specialty pharmacy, and that physician’s offices also charge about 23% more. However, these figures highlight how much insurers are billed, not necessarily how much patients ultimately pay.

Other evidence shows that white bagging raises costs for patients while reducing reimbursement for oncologists and saving insurance companies money.

A recent analysis in JAMA Network Open, which looked at 50 cancer drugs associated with the highest total spending from the 2020 Medicare Part B, found that mean insurance payments to providers were more than $2000 lower for drugs distributed under bagging than traditional buy and bill: $7405 vs $9547 per patient per month. Investigators found the same pattern in median insurance payments: $5746 vs $6681. Patients also paid more out-of-pocket each month with bagging vs buy and bill: $315 vs $145.

For patients with private insurance, “out-of-pocket costs were higher under bagging practice than the traditional buy-and-bill practice,” said lead author Ya-Chen Tina Shih, PhD, a professor in the department of radiation oncology at UCLA Health, Los Angeles.

White bagging is entirely for the profit of health insurers, specialty pharmacies, and pharmacy benefit managers, the middlemen who negotiate drug prices on behalf of payers.

Many people may not realize the underlying money-making strategies behind white bagging, explained Ted Okon, executive director for Community Oncology Alliance, which opposes the practice. Often, an insurer, pharmacy benefit manager, and mail order pharmacy involved in the process are all affiliated with the same corporation. In such cases, an insurer has a financial motive to control the source of medications and steer business to its affiliated pharmacies, Mr. Okon said.

When a single corporation owns numerous parts of the drug supply chain, insurers end up having “sway over what drug to use and then how the patient is going to get it,” Mr. Okon said. If the specialty pharmacy is a 340B contract pharmacy, it likely also receives a sizable discount on the drug and can make more money through white bagging.
 

 

 

Dangerous to Patients?

On the safety front, proponents of white bagging say the process is safe and efficient.

Specialty pharmacies are used only for prescription drugs that can be safely delivered, said AHIP spokesman David Allen.

In addition to having the same supply chain safety requirements as any other dispensing pharmacy, “specialty pharmacies also must meet additional safety requirements for specialty drugs” to ensure “the safe storage, handling, and dispensing of the drugs,” Mr. Allen explained.

However, oncologists argue that white bagging can be dangerous.

With white bagging, specialty pharmacies send a specified dose to practices, which does not allow practices to source and mix the drug themselves or make essential last-minute dose-related changes — something that happens every day in the clinic, said Debra Patt, MD, PhD, MBA, executive vice president for policy and strategy for Texas Oncology, Dallas.

White bagging also increases the risk for drug contamination, results in drug waste if the medication can’t be used, and can create delays in care.

Essentially, white bagging takes control away from oncologists and makes patient care more unpredictable and complex, explained Dr. Patt, president of the Texas Society of Clinical Oncology, Rockville, Maryland.

Dr. Patt, who does not allow white bagging in her practice, recalled a recent patient with metastatic breast cancer who came to the clinic for trastuzumab deruxtecan. The patient had been experiencing acute abdominal pain. After an exam and CT, Dr. Patt found the breast cancer had grown and moved into the patient’s liver.

“I had to discontinue that plan and change to a different chemotherapy,” she said. “If we had white bagged, that would have been a waste of several thousand dollars. Also, the patient would have to wait for the new medication to be white bagged, a delay that would be at least a week and the patient would have to come back at another time.”

When asked about the safety concerns associated with white bagging, Lemrey “Al” Carter, MS, PharmD, RPh, executive director of the National Association of Boards of Pharmacy (NABP), said the NABP “acknowledges that all these issues exist.

“It is unfortunate if patient care or costs are negatively impacted,” Dr. Carter said, adding that “boards of pharmacy can investigate if they are made aware of safety concerns at the pharmacy level. If a violation of the pharmacy laws or rules is found, boards can take action.”
 

More Legislation to Prevent Bagging

As white bagging mandates from insurance companies ramp up, more practices and states are banning it.

In the Association of Community Cancer Centers’ 2021 survey, 59% of members said their cancer program or practice does not allow white bagging.

At least 15 states have introduced legislation that restricts and/or prohibits white and brown bagging practices, according to a 2023 report by the Institute for Clinical and Economic Review. Some of the proposed laws would restrict mandates by stipulating that physicians are reimbursed at the contracted amount for clinician-administered drugs, whether obtained from a pharmacy or the manufacturer.

Louisiana, Vermont, and Minnesota were the first to enact anti–white bagging laws. Louisiana’s law, for example, enacted in 2021, bans white bagging and requires insurers to reimburse providers for physician-administered drugs if obtained from out-of-network pharmacies.

When the legislation passed, white bagging was just starting to enter the healthcare market in Louisiana, and the state wanted to act proactively, said Kathy W. Oubre, MS, CEO of the Pontchartrain Cancer Center, Covington, Louisiana, and president of the Coalition of Hematology and Oncology Practices, Mountain View, California.

“We recognized the growing concern around it,” Ms. Oubre said. The state legislature at the time included physicians and pharmacists who “really understood from a practice and patient perspective, the harm that policy could do.”

Ms. Oubre would like to see more legislation in other states and believes Louisiana’s law is a good model.

At the federal level, the American Hospital Association and American Society of Health-System Pharmacists have also urged the US Food and Drug Administration to take appropriate enforcement action to protect patients from white bagging.

Legislation that bars white bagging mandates is the most reasonable way to support timely and appropriate access to cancer care, Dr. Patt said. In the absence of such legislation, she said oncologists can only opt out of insurance contracts that may require the practice.

“That is a difficult position to put oncologists in,” she said.

A version of this article appeared on Medscape.com.

For years, oncologist John DiPersio, MD, PhD, had faced frustrating encounters with insurers that only cover medications through a process called white bagging.

Instead of the traditional buy-and-bill pathway where oncologists purchase specialty drugs, such as infusion medications, directly from the distributor or manufacturer, white bagging requires physicians to receive these drugs from a specialty pharmacy.

On its face, the differences may seem minor. However, as Dr. DiPersio knows well, the consequences for oncologists and patients are not.

White bagging, research showed, leads to higher costs for patients and lower reimbursement for oncology practices. The practice can also create safety issues for patients.

That is why Dr. DiPersio’s cancer center does not allow white bagging.

And when insurers refuse to reconsider the white bagging policy, his cancer team is left with few options.

“Sometimes, we have to redirect patients to other places,” said Dr. DiPersio, a bone marrow transplant specialist at Siteman Cancer Center, Washington University, St. Louis.

In emergency instances where patients cannot wait, Dr. DiPersio’s team will administer their own stock of a drug. In such cases, “we accept the fact that by not allowing white bagging, there may be nonpayment. We take the hit as far as cost.”

Increasingly, white bagging mandates are becoming harder for practices to avoid.

In a 2021 survey, 87% of Association of Community Cancer Centers members said white bagging has become an insurer mandate for some of their patients.

2023 analysis from Adam J. Fein, PhD, of Drug Channels Institute, Philadelphia, found that white bagging accounted for 17% of infused oncology product sourcing from clinics and 38% from hospital outpatient departments, up from 15% to 28% in 2019. Another practice called brown bagging, where specialty pharmacies send drugs directly to patients, creates many of the same issues but is much less prevalent than white bagging.

This change reflects “the broader battle over oncology margins” and insurers’ “attempts to shift costs to providers, patients, and manufacturers,” Dr. Fein wrote in his 2023 report.
 

White Bagging: Who Benefits?

At its core, white bagging changes how drugs are covered and reimbursed. Under buy and bill, drugs fall under a patient’s medical benefit. Oncologists purchase drugs directly from the manufacturer or distributor and receive reimbursement from the insurance company for both the cost of the drug as well as for administering it to patients.

Under white bagging, drugs fall under a patient’s pharmacy benefit. In these instances, a specialty pharmacy prepares the infusion ahead of time and ships it directly to the physician’s office or clinic. Because oncologists do not purchase the drug directly, they cannot bill insurers for it; instead, the pharmacy receives reimbursement for the drug and the provider is reimbursed for administering it.

Insurance companies argue that white bagging reduces patients’ out-of-pocket costs “by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” according to advocacy group America’s Health Insurance Plans (AHIP).

Data from AHIP suggested that hospitals mark up the price of cancer drugs considerably, charging about twice as much as a specialty pharmacy, and that physician’s offices also charge about 23% more. However, these figures highlight how much insurers are billed, not necessarily how much patients ultimately pay.

Other evidence shows that white bagging raises costs for patients while reducing reimbursement for oncologists and saving insurance companies money.

A recent analysis in JAMA Network Open, which looked at 50 cancer drugs associated with the highest total spending from the 2020 Medicare Part B, found that mean insurance payments to providers were more than $2000 lower for drugs distributed under bagging than traditional buy and bill: $7405 vs $9547 per patient per month. Investigators found the same pattern in median insurance payments: $5746 vs $6681. Patients also paid more out-of-pocket each month with bagging vs buy and bill: $315 vs $145.

For patients with private insurance, “out-of-pocket costs were higher under bagging practice than the traditional buy-and-bill practice,” said lead author Ya-Chen Tina Shih, PhD, a professor in the department of radiation oncology at UCLA Health, Los Angeles.

White bagging is entirely for the profit of health insurers, specialty pharmacies, and pharmacy benefit managers, the middlemen who negotiate drug prices on behalf of payers.

Many people may not realize the underlying money-making strategies behind white bagging, explained Ted Okon, executive director for Community Oncology Alliance, which opposes the practice. Often, an insurer, pharmacy benefit manager, and mail order pharmacy involved in the process are all affiliated with the same corporation. In such cases, an insurer has a financial motive to control the source of medications and steer business to its affiliated pharmacies, Mr. Okon said.

When a single corporation owns numerous parts of the drug supply chain, insurers end up having “sway over what drug to use and then how the patient is going to get it,” Mr. Okon said. If the specialty pharmacy is a 340B contract pharmacy, it likely also receives a sizable discount on the drug and can make more money through white bagging.
 

 

 

Dangerous to Patients?

On the safety front, proponents of white bagging say the process is safe and efficient.

Specialty pharmacies are used only for prescription drugs that can be safely delivered, said AHIP spokesman David Allen.

In addition to having the same supply chain safety requirements as any other dispensing pharmacy, “specialty pharmacies also must meet additional safety requirements for specialty drugs” to ensure “the safe storage, handling, and dispensing of the drugs,” Mr. Allen explained.

However, oncologists argue that white bagging can be dangerous.

With white bagging, specialty pharmacies send a specified dose to practices, which does not allow practices to source and mix the drug themselves or make essential last-minute dose-related changes — something that happens every day in the clinic, said Debra Patt, MD, PhD, MBA, executive vice president for policy and strategy for Texas Oncology, Dallas.

White bagging also increases the risk for drug contamination, results in drug waste if the medication can’t be used, and can create delays in care.

Essentially, white bagging takes control away from oncologists and makes patient care more unpredictable and complex, explained Dr. Patt, president of the Texas Society of Clinical Oncology, Rockville, Maryland.

Dr. Patt, who does not allow white bagging in her practice, recalled a recent patient with metastatic breast cancer who came to the clinic for trastuzumab deruxtecan. The patient had been experiencing acute abdominal pain. After an exam and CT, Dr. Patt found the breast cancer had grown and moved into the patient’s liver.

“I had to discontinue that plan and change to a different chemotherapy,” she said. “If we had white bagged, that would have been a waste of several thousand dollars. Also, the patient would have to wait for the new medication to be white bagged, a delay that would be at least a week and the patient would have to come back at another time.”

When asked about the safety concerns associated with white bagging, Lemrey “Al” Carter, MS, PharmD, RPh, executive director of the National Association of Boards of Pharmacy (NABP), said the NABP “acknowledges that all these issues exist.

“It is unfortunate if patient care or costs are negatively impacted,” Dr. Carter said, adding that “boards of pharmacy can investigate if they are made aware of safety concerns at the pharmacy level. If a violation of the pharmacy laws or rules is found, boards can take action.”
 

More Legislation to Prevent Bagging

As white bagging mandates from insurance companies ramp up, more practices and states are banning it.

In the Association of Community Cancer Centers’ 2021 survey, 59% of members said their cancer program or practice does not allow white bagging.

At least 15 states have introduced legislation that restricts and/or prohibits white and brown bagging practices, according to a 2023 report by the Institute for Clinical and Economic Review. Some of the proposed laws would restrict mandates by stipulating that physicians are reimbursed at the contracted amount for clinician-administered drugs, whether obtained from a pharmacy or the manufacturer.

Louisiana, Vermont, and Minnesota were the first to enact anti–white bagging laws. Louisiana’s law, for example, enacted in 2021, bans white bagging and requires insurers to reimburse providers for physician-administered drugs if obtained from out-of-network pharmacies.

When the legislation passed, white bagging was just starting to enter the healthcare market in Louisiana, and the state wanted to act proactively, said Kathy W. Oubre, MS, CEO of the Pontchartrain Cancer Center, Covington, Louisiana, and president of the Coalition of Hematology and Oncology Practices, Mountain View, California.

“We recognized the growing concern around it,” Ms. Oubre said. The state legislature at the time included physicians and pharmacists who “really understood from a practice and patient perspective, the harm that policy could do.”

Ms. Oubre would like to see more legislation in other states and believes Louisiana’s law is a good model.

At the federal level, the American Hospital Association and American Society of Health-System Pharmacists have also urged the US Food and Drug Administration to take appropriate enforcement action to protect patients from white bagging.

Legislation that bars white bagging mandates is the most reasonable way to support timely and appropriate access to cancer care, Dr. Patt said. In the absence of such legislation, she said oncologists can only opt out of insurance contracts that may require the practice.

“That is a difficult position to put oncologists in,” she said.

A version of this article appeared on Medscape.com.

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Psilocybin-Assisted Group Therapy Promising for Depression in Cancer Patients

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Fri, 01/19/2024 - 14:40

 

TOPLINE:

A single dose of psilocybin administered in a group setting with one-on-one psychological support was associated with a significant and lasting reduction in depression severity among adults with cancer and major depressive disorder, a small study shows.

METHODOLOGY:

  • Depression remains common in patients with cancer, and common treatment approaches — antidepressants and psychotherapy — have demonstrated limited success.
  • Researchers explored the safety, feasibility, and efficacy of psilocybin-assisted group therapy in 30 patients with major depressive disorder and cancer — about half with earlier-stage disease and half with metastatic disease.
  • In this single-center, open-label, phase 2 study, participants received one-on-one and group therapy sessions before, during, and after receiving a single 25-mg psilocybin dose.
  • Alongside individual therapy sessions, each cohort of three to four participants received group sessions guided by a therapist who provided educational material and worked to foster trust among participants.

TAKEAWAY:

  • Participants experienced a significant reduction in depression severity, demonstrating a 19.1-point reduction in Montgomery-Asberg Depression Rating Scale scores from baseline to follow-up at week 8.
  • Overall, 80% of patients showed a lasting response to psilocybin treatment and 50% showed full remission of depressive symptoms by week 1, which persisted for at least 8 weeks.
  • The approach was effective for patients with curable and noncurable cancer — with almost 80% in the curable group and 62% in the noncurable group showing clinically meaningful declines in depressive symptoms. The researchers also noted improvements in patients’ anxiety, pain, demoralization, disability, and spiritual well-being.
  • No suicidality or other serious treatment-related adverse events occurred; treatment-related nausea and headache were generally mild and expected.

IN PRACTICE:

“Beyond tolerability, psilocybin therapy led to clinically meaningful reductions in depressive symptoms,” the authors concluded. “To our knowledge, this is the first study to show the feasibility of a group-therapy approach for psilocybin‐assisted treatment in patients with cancer. This innovative framework offers increased scalability and dissemination of psilocybin treatment in real‐world settings.”

Among the 28 participants available for exit interviews, the authors reported that, overall, “participants described that the group/simultaneous model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration.”

SOURCE:

The study, led by Manish Agrawal, MD, Sunstone Therapies, Rockville, Maryland, was published online on December 21, 2023, in Cancer, along with an editorial and related article on patient acceptability of psilocybin-assisted group therapy.

LIMITATIONS:

The study lacked a control group, and the sample size was small and lacked diversity. The study was also not powered to statistically adjust efficacy measures on a possible group effect.

DISCLOSURES:

The study was funded in part by Compass Pathways. Some authors reported various relationships with Compass Pathways and Sunstone Therapies.

A version of this article appeared on Medscape.com.

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TOPLINE:

A single dose of psilocybin administered in a group setting with one-on-one psychological support was associated with a significant and lasting reduction in depression severity among adults with cancer and major depressive disorder, a small study shows.

METHODOLOGY:

  • Depression remains common in patients with cancer, and common treatment approaches — antidepressants and psychotherapy — have demonstrated limited success.
  • Researchers explored the safety, feasibility, and efficacy of psilocybin-assisted group therapy in 30 patients with major depressive disorder and cancer — about half with earlier-stage disease and half with metastatic disease.
  • In this single-center, open-label, phase 2 study, participants received one-on-one and group therapy sessions before, during, and after receiving a single 25-mg psilocybin dose.
  • Alongside individual therapy sessions, each cohort of three to four participants received group sessions guided by a therapist who provided educational material and worked to foster trust among participants.

TAKEAWAY:

  • Participants experienced a significant reduction in depression severity, demonstrating a 19.1-point reduction in Montgomery-Asberg Depression Rating Scale scores from baseline to follow-up at week 8.
  • Overall, 80% of patients showed a lasting response to psilocybin treatment and 50% showed full remission of depressive symptoms by week 1, which persisted for at least 8 weeks.
  • The approach was effective for patients with curable and noncurable cancer — with almost 80% in the curable group and 62% in the noncurable group showing clinically meaningful declines in depressive symptoms. The researchers also noted improvements in patients’ anxiety, pain, demoralization, disability, and spiritual well-being.
  • No suicidality or other serious treatment-related adverse events occurred; treatment-related nausea and headache were generally mild and expected.

IN PRACTICE:

“Beyond tolerability, psilocybin therapy led to clinically meaningful reductions in depressive symptoms,” the authors concluded. “To our knowledge, this is the first study to show the feasibility of a group-therapy approach for psilocybin‐assisted treatment in patients with cancer. This innovative framework offers increased scalability and dissemination of psilocybin treatment in real‐world settings.”

Among the 28 participants available for exit interviews, the authors reported that, overall, “participants described that the group/simultaneous model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration.”

SOURCE:

The study, led by Manish Agrawal, MD, Sunstone Therapies, Rockville, Maryland, was published online on December 21, 2023, in Cancer, along with an editorial and related article on patient acceptability of psilocybin-assisted group therapy.

LIMITATIONS:

The study lacked a control group, and the sample size was small and lacked diversity. The study was also not powered to statistically adjust efficacy measures on a possible group effect.

DISCLOSURES:

The study was funded in part by Compass Pathways. Some authors reported various relationships with Compass Pathways and Sunstone Therapies.

A version of this article appeared on Medscape.com.

 

TOPLINE:

A single dose of psilocybin administered in a group setting with one-on-one psychological support was associated with a significant and lasting reduction in depression severity among adults with cancer and major depressive disorder, a small study shows.

METHODOLOGY:

  • Depression remains common in patients with cancer, and common treatment approaches — antidepressants and psychotherapy — have demonstrated limited success.
  • Researchers explored the safety, feasibility, and efficacy of psilocybin-assisted group therapy in 30 patients with major depressive disorder and cancer — about half with earlier-stage disease and half with metastatic disease.
  • In this single-center, open-label, phase 2 study, participants received one-on-one and group therapy sessions before, during, and after receiving a single 25-mg psilocybin dose.
  • Alongside individual therapy sessions, each cohort of three to four participants received group sessions guided by a therapist who provided educational material and worked to foster trust among participants.

TAKEAWAY:

  • Participants experienced a significant reduction in depression severity, demonstrating a 19.1-point reduction in Montgomery-Asberg Depression Rating Scale scores from baseline to follow-up at week 8.
  • Overall, 80% of patients showed a lasting response to psilocybin treatment and 50% showed full remission of depressive symptoms by week 1, which persisted for at least 8 weeks.
  • The approach was effective for patients with curable and noncurable cancer — with almost 80% in the curable group and 62% in the noncurable group showing clinically meaningful declines in depressive symptoms. The researchers also noted improvements in patients’ anxiety, pain, demoralization, disability, and spiritual well-being.
  • No suicidality or other serious treatment-related adverse events occurred; treatment-related nausea and headache were generally mild and expected.

IN PRACTICE:

“Beyond tolerability, psilocybin therapy led to clinically meaningful reductions in depressive symptoms,” the authors concluded. “To our knowledge, this is the first study to show the feasibility of a group-therapy approach for psilocybin‐assisted treatment in patients with cancer. This innovative framework offers increased scalability and dissemination of psilocybin treatment in real‐world settings.”

Among the 28 participants available for exit interviews, the authors reported that, overall, “participants described that the group/simultaneous model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration.”

SOURCE:

The study, led by Manish Agrawal, MD, Sunstone Therapies, Rockville, Maryland, was published online on December 21, 2023, in Cancer, along with an editorial and related article on patient acceptability of psilocybin-assisted group therapy.

LIMITATIONS:

The study lacked a control group, and the sample size was small and lacked diversity. The study was also not powered to statistically adjust efficacy measures on a possible group effect.

DISCLOSURES:

The study was funded in part by Compass Pathways. Some authors reported various relationships with Compass Pathways and Sunstone Therapies.

A version of this article appeared on Medscape.com.

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CMS Okays Payment for Novel AI Prostate Test

Article Type
Changed
Tue, 01/16/2024 - 16:20

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

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Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

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SUDs rates highest in head, neck, and gastric cancer survivors

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Tue, 01/16/2024 - 16:09

Nearly 10% of survivors of head, neck, esophageal, and gastric cancers experienced active substance use disorders, based on data from more than 6,000 individuals.

The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.

“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.

In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.

The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.

Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).

Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.

Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).

The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
 

Limitations and Implications

The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.

“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.

“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
 

 

 

Integrated care is needed

“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.

Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
 

Recognize risk factors

“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.

The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
 

Individualize risk assessment

“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.

As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.

The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.

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Nearly 10% of survivors of head, neck, esophageal, and gastric cancers experienced active substance use disorders, based on data from more than 6,000 individuals.

The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.

“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.

In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.

The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.

Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).

Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.

Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).

The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
 

Limitations and Implications

The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.

“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.

“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
 

 

 

Integrated care is needed

“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.

Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
 

Recognize risk factors

“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.

The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
 

Individualize risk assessment

“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.

As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.

The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.

Nearly 10% of survivors of head, neck, esophageal, and gastric cancers experienced active substance use disorders, based on data from more than 6,000 individuals.

The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.

“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.

In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.

The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.

Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).

Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.

Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).

The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
 

Limitations and Implications

The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.

“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.

“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
 

 

 

Integrated care is needed

“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.

Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
 

Recognize risk factors

“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.

The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
 

Individualize risk assessment

“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.

As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.

The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.

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