AVAHO

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

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

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

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

The Food and Drug Administration approved a new colony-stimulating factor, efbemalenograstim alfa (Ryzneuta, Evive Biotech), to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive anticancer drugs.

Efbemalenograstim joins other agents already on the U.S. market, including pegfilgrastim (Neulasta), that aim to reduce the incidence of chemotherapy-induced febrile neutropenia.

The approval of efbemalenograstim was based on two randomized trials. The first included 122 women with either metastatic or nonmetastatic breast cancer who were receiving doxorubicin and docetaxel. These patients were randomly assigned to receive either one subcutaneous injection of efbemalenograstim or placebo on the second day of their first chemotherapy cycle. All patients received efbemalenograstim on the second day of cycles two through four.

The mean duration of grade 4 neutropenia in the first cycle was 1.4 days with efbemalenograstim versus 4.3 days with placebo. Only 4.8% of patients who received efbemalenograstim experienced chemotherapy-induced febrile neutropenia, compared with 25.6% who received the placebo.

The new agent went up against pegfilgrastim in the second trial, which included 393 women who received docetaxel and cyclophosphamide as treatment for nonmetastatic breast cancer. These patients were randomly assigned to receive either a single subcutaneous injection of efbemalenograstim or pegfilgrastim on the second day of each cycle.

During the first cycle, patients in both arms of the trial experienced a mean of 0.2 days of grade 4 neutropenia.

The most common side effects associated with efbemalenograstim were nausea, anemia, and thrombocytopenia. Similar to pegfilgrastim’s label, efbemalenograstim’s label warns of possible splenic rupture, respiratory distress syndrome, sickle cell crisis, and other serious adverse events.

The FDA recommends a dose of 20 mg subcutaneous once per chemotherapy cycle.

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

CHICAGO – The US Department of Veterans Affairs (VA) has developed clinical pathways to guide its clinicians through cancer care, but they should not be considered mandatory strategies, a top VA cancer director told colleagues at the 2023 annual meeting of the Association of VA Hematology/Oncology.

“They’re not a cookbook for how to practice oncology,” said Michael Kelley, MD, the VA National Program Director for Oncology, Professor of Medicine at Duke University, and Chief of Hematology and Oncology at the Durham VA Medical Center. “You cannot look at the pathway and think that you know how to practice. It is a preferred-decision flow map—not a requirement to do that. We expect that all providers will be off the pathways some of the time and most of the time, they will be on there.”

The VA has an extensive series of clinical pathways in oncology that are designed to help clinicians navigate through the treatment of 20 types of cancer, including common types—breast, lung, and colon—and rarer types, such as salivary gland and biliary tract cancer. Many of the pathways have been updated within just the past few months, and more are in the works.

The pathways are developed through subject-matter expert groups made up of experts from National Cancer Institute–designated cancer centers, Kelley said. “The pathway is published as a PDF document on internally and externally facing websites, then it's built into the medical record system.” Clinicians who diverge from the pathways have to note this in the health record system, enter reasons why, and provide the alternative care strategy, Kelley explained.

Moving forward, the VA is “committed to doing a formal review of all the pathways at least quarterly, and we will do ad hoc reviews and alterations as information merits.” He said, “There are hundreds of oncology providers in the VA, and we want everyone to have an opportunity to have input. That's your opportunity: We do read every comment, and we'll actually generate a response to every comment.”

CHICAGO – The US Department of Veterans Affairs (VA) has developed clinical pathways to guide its clinicians through cancer care, but they should not be considered mandatory strategies, a top VA cancer director told colleagues at the 2023 annual meeting of the Association of VA Hematology/Oncology.

“They’re not a cookbook for how to practice oncology,” said Michael Kelley, MD, the VA National Program Director for Oncology, Professor of Medicine at Duke University, and Chief of Hematology and Oncology at the Durham VA Medical Center. “You cannot look at the pathway and think that you know how to practice. It is a preferred-decision flow map—not a requirement to do that. We expect that all providers will be off the pathways some of the time and most of the time, they will be on there.”

The VA has an extensive series of clinical pathways in oncology that are designed to help clinicians navigate through the treatment of 20 types of cancer, including common types—breast, lung, and colon—and rarer types, such as salivary gland and biliary tract cancer. Many of the pathways have been updated within just the past few months, and more are in the works.

The pathways are developed through subject-matter expert groups made up of experts from National Cancer Institute–designated cancer centers, Kelley said. “The pathway is published as a PDF document on internally and externally facing websites, then it's built into the medical record system.” Clinicians who diverge from the pathways have to note this in the health record system, enter reasons why, and provide the alternative care strategy, Kelley explained.

Moving forward, the VA is “committed to doing a formal review of all the pathways at least quarterly, and we will do ad hoc reviews and alterations as information merits.” He said, “There are hundreds of oncology providers in the VA, and we want everyone to have an opportunity to have input. That's your opportunity: We do read every comment, and we'll actually generate a response to every comment.”

CHICAGO – The US Department of Veterans Affairs (VA) has developed clinical pathways to guide its clinicians through cancer care, but they should not be considered mandatory strategies, a top VA cancer director told colleagues at the 2023 annual meeting of the Association of VA Hematology/Oncology.

“They’re not a cookbook for how to practice oncology,” said Michael Kelley, MD, the VA National Program Director for Oncology, Professor of Medicine at Duke University, and Chief of Hematology and Oncology at the Durham VA Medical Center. “You cannot look at the pathway and think that you know how to practice. It is a preferred-decision flow map—not a requirement to do that. We expect that all providers will be off the pathways some of the time and most of the time, they will be on there.”

The VA has an extensive series of clinical pathways in oncology that are designed to help clinicians navigate through the treatment of 20 types of cancer, including common types—breast, lung, and colon—and rarer types, such as salivary gland and biliary tract cancer. Many of the pathways have been updated within just the past few months, and more are in the works.

The pathways are developed through subject-matter expert groups made up of experts from National Cancer Institute–designated cancer centers, Kelley said. “The pathway is published as a PDF document on internally and externally facing websites, then it's built into the medical record system.” Clinicians who diverge from the pathways have to note this in the health record system, enter reasons why, and provide the alternative care strategy, Kelley explained.

Moving forward, the VA is “committed to doing a formal review of all the pathways at least quarterly, and we will do ad hoc reviews and alterations as information merits.” He said, “There are hundreds of oncology providers in the VA, and we want everyone to have an opportunity to have input. That's your opportunity: We do read every comment, and we'll actually generate a response to every comment.”

TOPLINE:

Getting patients to return unused oral anticancer drugs to the pharmacy and then having the pharmacy redispense those medications that meet quality standards is a promising strategy to save money and reduce waste, a Dutch study has found.

METHODOLOGY:

• Ongoing drug shortages and growing drug prices contribute to access issues in oncology.
• Researchers compared the reduction in drug waste and cost savings from redispensing oral anticancer drugs versus the standard practice of disposing of them.
• Outpatient pharmacies at four Dutch hospitals participated. A total of 1,071 patients with cancer receiving oral anticancer drugs for at-home use were given special packaging for returning unused medication to the pharmacy.
• The pharmacy ensured the quality of returned drugs based on authenticity, appearance, remaining shelf-life, and adequate storage temperature.

TAKEAWAY:

• A total of 13,069 oral anticancer drug packages, containing an average of 27 daily doses per package, were dispensed during the study period.
• Overall, 16% of patients (n = 171) returned 335 (2.6%) unused oral anticancer drug packages, of which 68% were redispensed after passing quality control.
• Redispensing unused oral anticancer drugs reduced waste by 68%, compared with disposing of them, and provided a mean net annual cost savings of €576 (U.S. $682) per patient per year.
• When just those patients who took targeted oral anticancer drugs for up to 24 months were looked at, the mean net annual cost savings associated with the quality check protocol increased to €934 (U.S. $1,019) per patient or of only the visual quality check was €1,348 (U.S. $1,474) per patient.

IN PRACTICE:

“New strategies targeting waste are required to improve financial and ecologic sustainability of expensive therapies, such as oral anticancer drugs, that frequently remain unused by patients,” the authors write. “These findings provide a waste-minimizing strategy to contribute to sustainable and affordable access to drugs.”

SOURCE:

The study, by Elisabeth M. Smale, PharmD, of Radboud University Medical Center, the Netherlands, and colleagues, was published online  in JAMA Oncology.

LIMITATIONS:

Novel drugs are substantially more expensive in the United States, and the Dutch findings might underestimate potential cost savings generated through redispensing programs in the United States. Participants were prompted to return unused oral anticancer drugs through reminders at the pharmacy, but all such drugs may not have been returned.

DISCLOSURES:

The study was funded by ZonMw, the Dutch national organization for health research and development. The authors have disclosed no relevant financial relationships.

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

TOPLINE:

Getting patients to return unused oral anticancer drugs to the pharmacy and then having the pharmacy redispense those medications that meet quality standards is a promising strategy to save money and reduce waste, a Dutch study has found.

METHODOLOGY:

• Ongoing drug shortages and growing drug prices contribute to access issues in oncology.
• Researchers compared the reduction in drug waste and cost savings from redispensing oral anticancer drugs versus the standard practice of disposing of them.
• Outpatient pharmacies at four Dutch hospitals participated. A total of 1,071 patients with cancer receiving oral anticancer drugs for at-home use were given special packaging for returning unused medication to the pharmacy.
• The pharmacy ensured the quality of returned drugs based on authenticity, appearance, remaining shelf-life, and adequate storage temperature.

TAKEAWAY:

• A total of 13,069 oral anticancer drug packages, containing an average of 27 daily doses per package, were dispensed during the study period.
• Overall, 16% of patients (n = 171) returned 335 (2.6%) unused oral anticancer drug packages, of which 68% were redispensed after passing quality control.
• Redispensing unused oral anticancer drugs reduced waste by 68%, compared with disposing of them, and provided a mean net annual cost savings of €576 (U.S. $682) per patient per year.
• When just those patients who took targeted oral anticancer drugs for up to 24 months were looked at, the mean net annual cost savings associated with the quality check protocol increased to €934 (U.S. $1,019) per patient or of only the visual quality check was €1,348 (U.S. $1,474) per patient.

IN PRACTICE:

“New strategies targeting waste are required to improve financial and ecologic sustainability of expensive therapies, such as oral anticancer drugs, that frequently remain unused by patients,” the authors write. “These findings provide a waste-minimizing strategy to contribute to sustainable and affordable access to drugs.”

SOURCE:

The study, by Elisabeth M. Smale, PharmD, of Radboud University Medical Center, the Netherlands, and colleagues, was published online  in JAMA Oncology.

LIMITATIONS:

Novel drugs are substantially more expensive in the United States, and the Dutch findings might underestimate potential cost savings generated through redispensing programs in the United States. Participants were prompted to return unused oral anticancer drugs through reminders at the pharmacy, but all such drugs may not have been returned.

DISCLOSURES:

The study was funded by ZonMw, the Dutch national organization for health research and development. The authors have disclosed no relevant financial relationships.

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

TOPLINE:

Getting patients to return unused oral anticancer drugs to the pharmacy and then having the pharmacy redispense those medications that meet quality standards is a promising strategy to save money and reduce waste, a Dutch study has found.

METHODOLOGY:

• Ongoing drug shortages and growing drug prices contribute to access issues in oncology.
• Researchers compared the reduction in drug waste and cost savings from redispensing oral anticancer drugs versus the standard practice of disposing of them.
• Outpatient pharmacies at four Dutch hospitals participated. A total of 1,071 patients with cancer receiving oral anticancer drugs for at-home use were given special packaging for returning unused medication to the pharmacy.
• The pharmacy ensured the quality of returned drugs based on authenticity, appearance, remaining shelf-life, and adequate storage temperature.

TAKEAWAY:

• A total of 13,069 oral anticancer drug packages, containing an average of 27 daily doses per package, were dispensed during the study period.
• Overall, 16% of patients (n = 171) returned 335 (2.6%) unused oral anticancer drug packages, of which 68% were redispensed after passing quality control.
• Redispensing unused oral anticancer drugs reduced waste by 68%, compared with disposing of them, and provided a mean net annual cost savings of €576 (U.S. $682) per patient per year.
• When just those patients who took targeted oral anticancer drugs for up to 24 months were looked at, the mean net annual cost savings associated with the quality check protocol increased to €934 (U.S. $1,019) per patient or of only the visual quality check was €1,348 (U.S. $1,474) per patient.

IN PRACTICE:

“New strategies targeting waste are required to improve financial and ecologic sustainability of expensive therapies, such as oral anticancer drugs, that frequently remain unused by patients,” the authors write. “These findings provide a waste-minimizing strategy to contribute to sustainable and affordable access to drugs.”

SOURCE:

The study, by Elisabeth M. Smale, PharmD, of Radboud University Medical Center, the Netherlands, and colleagues, was published online  in JAMA Oncology.

LIMITATIONS:

Novel drugs are substantially more expensive in the United States, and the Dutch findings might underestimate potential cost savings generated through redispensing programs in the United States. Participants were prompted to return unused oral anticancer drugs through reminders at the pharmacy, but all such drugs may not have been returned.

DISCLOSURES:

The study was funded by ZonMw, the Dutch national organization for health research and development. The authors have disclosed no relevant financial relationships.

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

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

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

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

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

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

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

TOPLINE:

Proctectomy and other surgeries are falling out of favor to treat stage II and III rectal cancer in the United States.

METHODOLOGY:

• The National Comprehensive Cancer Network endorses watchful waiting, instead of surgery, when patients with rectal cancer have a complete clinical response to neoadjuvant therapy, but it’s unclear how often patients and providers opt for this organ preservation approach.
• To find out, investigators reviewed 175,545 adults in the National Cancer Database treated for rectal adenocarcinoma from 2006 to 2020.
• The research team assessed changes in the proportion of patients who were treated with chemotherapy and/or radiation without tumor resection, transanal local excision, or removal of the rectum. 
• Patients had a mean age of 63 years, 39.7% were women, 17.4% had stage 1 disease, 24.7% had stage 2A-C disease, and 32.1% had stage 3A-C tumors; tumor stage was unknown in just over a quarter of patients.

TAKEAWAY:

• The absolute annual proportion of organ preservation increased by more than 50% from 18.4% in 2006 to 28.2% in 2020.
• In that time frame, organ preservation increased from 19.5% to 32.5% – a percent increase of about 67% – for patients with stage 2A-C disease, 16.2% to 29.1% – a percent increase of about 80% – for patients with stage 3A-C disease, and 16.5% to 26.6% – a percent increase of about 60% – for those with unknown stages.
• However, the rate of proctectomies increased by 6.1 percentage points, or by about 30%, among patients with stage I rectal cancer – from 20.3% to 26.4%.
• Among patients who did have surgery, the proportion who had complete pathologic responses to neoadjuvant therapy nearly tripled, increasing from 6.5% to 18.8%.

IN PRACTICE:

“This case series shows that rectal cancer is increasingly being managed medically, especially among patients whose treatment historically relied on proctectomy,” the authors concluded. However, protocols to standardize the approach are lacking, which is why “establishing quality standards for organ preservation is a pressing issue that should involve all relevant stakeholders, including patients.”

SOURCE:

The study, led by Anthony Loria, MD, MSCI, of the University of Rochester (N.Y.), was published online in JAMA Oncology.

LIMITATIONS:

The percentage of people who needed surgery for recurrence, patient and facility factors associated with organ preservation, and overall survival outcomes were not addressed.

DISCLOSURES:

No external funding was reported, and the investigators reported no relevant financial relationships.

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

TOPLINE:

Proctectomy and other surgeries are falling out of favor to treat stage II and III rectal cancer in the United States.

METHODOLOGY:

• The National Comprehensive Cancer Network endorses watchful waiting, instead of surgery, when patients with rectal cancer have a complete clinical response to neoadjuvant therapy, but it’s unclear how often patients and providers opt for this organ preservation approach.
• To find out, investigators reviewed 175,545 adults in the National Cancer Database treated for rectal adenocarcinoma from 2006 to 2020.
• The research team assessed changes in the proportion of patients who were treated with chemotherapy and/or radiation without tumor resection, transanal local excision, or removal of the rectum. 
• Patients had a mean age of 63 years, 39.7% were women, 17.4% had stage 1 disease, 24.7% had stage 2A-C disease, and 32.1% had stage 3A-C tumors; tumor stage was unknown in just over a quarter of patients.

TAKEAWAY:

• The absolute annual proportion of organ preservation increased by more than 50% from 18.4% in 2006 to 28.2% in 2020.
• In that time frame, organ preservation increased from 19.5% to 32.5% – a percent increase of about 67% – for patients with stage 2A-C disease, 16.2% to 29.1% – a percent increase of about 80% – for patients with stage 3A-C disease, and 16.5% to 26.6% – a percent increase of about 60% – for those with unknown stages.
• However, the rate of proctectomies increased by 6.1 percentage points, or by about 30%, among patients with stage I rectal cancer – from 20.3% to 26.4%.
• Among patients who did have surgery, the proportion who had complete pathologic responses to neoadjuvant therapy nearly tripled, increasing from 6.5% to 18.8%.

IN PRACTICE:

“This case series shows that rectal cancer is increasingly being managed medically, especially among patients whose treatment historically relied on proctectomy,” the authors concluded. However, protocols to standardize the approach are lacking, which is why “establishing quality standards for organ preservation is a pressing issue that should involve all relevant stakeholders, including patients.”

SOURCE:

The study, led by Anthony Loria, MD, MSCI, of the University of Rochester (N.Y.), was published online in JAMA Oncology.

LIMITATIONS:

The percentage of people who needed surgery for recurrence, patient and facility factors associated with organ preservation, and overall survival outcomes were not addressed.

DISCLOSURES:

No external funding was reported, and the investigators reported no relevant financial relationships.

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

TOPLINE:

Proctectomy and other surgeries are falling out of favor to treat stage II and III rectal cancer in the United States.

METHODOLOGY:

• The National Comprehensive Cancer Network endorses watchful waiting, instead of surgery, when patients with rectal cancer have a complete clinical response to neoadjuvant therapy, but it’s unclear how often patients and providers opt for this organ preservation approach.
• To find out, investigators reviewed 175,545 adults in the National Cancer Database treated for rectal adenocarcinoma from 2006 to 2020.
• The research team assessed changes in the proportion of patients who were treated with chemotherapy and/or radiation without tumor resection, transanal local excision, or removal of the rectum. 
• Patients had a mean age of 63 years, 39.7% were women, 17.4% had stage 1 disease, 24.7% had stage 2A-C disease, and 32.1% had stage 3A-C tumors; tumor stage was unknown in just over a quarter of patients.

TAKEAWAY:

• The absolute annual proportion of organ preservation increased by more than 50% from 18.4% in 2006 to 28.2% in 2020.
• In that time frame, organ preservation increased from 19.5% to 32.5% – a percent increase of about 67% – for patients with stage 2A-C disease, 16.2% to 29.1% – a percent increase of about 80% – for patients with stage 3A-C disease, and 16.5% to 26.6% – a percent increase of about 60% – for those with unknown stages.
• However, the rate of proctectomies increased by 6.1 percentage points, or by about 30%, among patients with stage I rectal cancer – from 20.3% to 26.4%.
• Among patients who did have surgery, the proportion who had complete pathologic responses to neoadjuvant therapy nearly tripled, increasing from 6.5% to 18.8%.

IN PRACTICE:

“This case series shows that rectal cancer is increasingly being managed medically, especially among patients whose treatment historically relied on proctectomy,” the authors concluded. However, protocols to standardize the approach are lacking, which is why “establishing quality standards for organ preservation is a pressing issue that should involve all relevant stakeholders, including patients.”

SOURCE:

The study, led by Anthony Loria, MD, MSCI, of the University of Rochester (N.Y.), was published online in JAMA Oncology.

LIMITATIONS:

The percentage of people who needed surgery for recurrence, patient and facility factors associated with organ preservation, and overall survival outcomes were not addressed.

DISCLOSURES:

No external funding was reported, and the investigators reported no relevant financial relationships.

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

Breast cancer has a worse prognosis when diagnosed during pregnancy or postpartum. Methods for early detection are needed, as evidenced every day in the multidisciplinary unit for treating pregnancy-associated breast cancer, which operates within the breast unit at the Vall d’Hebron University Hospital in Barcelona.

The team working in this field is led by Cristina Saura, PhD, who is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO). The results of a study recently published in Cancer Discovery show, for the first time, that breast milk from breast cancer patients contains circulating tumor DNA that can be detected by a liquid biopsy of the milk.

Dr. Saura explained in an interview why they began to pursue this research, which, in one sense, fell into their laps. “In this case, it arose from the concerns of a breast cancer patient who was diagnosed while pregnant with her third daughter. She was actually the one who came up with the idea for the project. She was worried that she had transmitted the tumor through her breast milk to her second daughter while breastfeeding. She had been breastfeeding for a long time and had stretched it out until shortly before she was diagnosed with breast cancer. So she brought us a sample of breast milk that she had stored in her freezer.

“So, thanks to her, that’s where our project started. Though we knew that breast cancer is not transmitted through breast milk, we decided to test the sample and look for markers that could help our research. In the end, when we analyzed the patient’s breast milk, we found DNA with the same mutation that was present in her tumor,” explained Dr. Saura. She noted that the breast milk they analyzed had been frozen for more than a year before the patient’s cancer diagnosis.

In terms of methodology, Ana Vivancos, PhD, head of the VHIO cancer genomics group and also one of the authors of the study, explained that they used two techniques to analyze the breast milk and blood samples: next-generation sequencing and droplet digital polymerase chain reaction. These methods confirmed the presence of ctDNA in the breast milk.
 

High-sensitivity genomic panel

“We were able to detect tumor mutations in milk samples from 13 of the 15 patients with breast cancer who were tested, while circulating tumor DNA was detected in only one of all the blood samples that were collected at the same time,” said Dr. Vivancos. “The samples from the two patients for whom no mutation was detected were discovered to be colostrum that had been collected during the first few hours of lactation.”

As a next step to make this finding practically useful, the research team designed a genomic panel using next-generation sequencing as a potential method for early detection of breast cancer. “We’ve developed a panel that uses hybrid capture chemistry and unique molecular identifiers that ensure better sensitivity during next-generation sequencing. The panel has been calibrated, based on the existing literature, to detect the genes that are most frequently mutated in breast cancer in young women under 45 years old.”

According to Dr. Vivancos, the sensitivity of this panel exceeds 70%. This means that for all the patient samples analyzed using this panel, 7 out of 10 cases are detected with 100% specificity.

“In practice, the panel design allows us to detect mutations in more than 95% of breast cancer cases in women under 45 years old. Therefore, using this panel for early detection of this type of tumor during lactation should contribute to addressing a medical need that, until today, has gone unmet,” noted Dr. Vivancos.

As for this unresolved need, Dr. Saura explained that there is currently no system or tool available to allow early suspicion of breast tumors in pregnant women prior to diagnosis. “That’s exactly the goal of this research: to screen for breast cancer in women who have just given birth. Now, it needs to be validated in a larger group of women in a clinical trial.”
 

More direct contact with tumor cells

In Dr. Saura’s opinion, in Spain, just like taking a small blood sample from newborns in a heel-prick test to rule out metabolic diseases, milk samples could be taken from women who give birth to rule out or diagnose breast cancer.

As to the potential advantages that breast milk liquid biopsy could have over similar techniques like blood liquid biopsy, Dr. Vivancos pointed to the results of her study: “We have seen that breast milk liquid biopsy was positive for the presence of circulating tumor DNA in 87% of cases, whereas blood only revealed the presence of this marker in 8% of cases. This difference indicates that breast milk is a biofluid that is in more direct contact with tumor cells and therefore will be more informative in earlier stages.”

Dr. Saura explained that the data does not lie when it comes to these tumors in pregnant or postpartum women. “In general, they tend to have a worse prognosis because, in most cases, they are diagnosed in advanced stages. Furthermore, it is typically assumed that the physiological changes in the breasts during gestation and lactation, which are considered to be normal, may hide a developing tumor. The fact is that postpartum breast cancer, understood to be the 10 years after delivery, accounts for 40%-45% of breast cancer cases diagnosed before age 45.”

The researchers plan to continue this project. “Our next step to confirm the usefulness of breast milk as a new tool for liquid biopsy for early detection of breast cancer during the postpartum period is to perform this noninvasive test in thousands of women,” said Dr. Saura.
 

Goal: Standardize the test as a screening method

“Based on the results we’ve published, we’re starting a study aimed at collecting breast milk samples from 5,000 healthy women around the world who became pregnant at age 40 or older, or who got pregnant at any age and carry mutations that increase their risk of breast cancer,” Dr. Saura added.

When asked when they expect to have preliminary results from this new study, Dr. Saura stated that it’s not yet possible to say exactly when. “We’re still waiting for funding to continue this project, but we continue performing analyses on a case-by-case basis. Of course, if we detect any abnormalities in these women, we will follow the established protocol to confirm diagnosis and start treatment if necessary.”

When asked whether it is reasonable to expect breast milk liquid biopsy to become normalized as a screening method for women of childbearing age who have a history or risk factors for developing breast cancer, Dr. Vivancos said, “That’s the scenario we see in the future and what we wish to contribute toward by providing scientific evidence to make it a reality.”

“For now, our goal is to validate whether circulating tumor DNA can be detected by breast milk liquid biopsy even before breast cancer can be diagnosed using conventional imaging techniques. If we can validate these preliminary results, we will be able to detect breast cancer early using a noninvasive test like breast milk liquid biopsy,” explained Saura.

Lastly, and in view of the issues that are still unresolved when it comes to the detection and treatment of breast cancer during pregnancy, Dr. Saura highlighted the emotional impact that a diagnosis of pregnancy-related cancer has on women and on those close to them. “But the first thing they need to know is that diagnosis is not necessarily synonymous with termination of the pregnancy. On the contrary, this tumor can be treated during pregnancy, since surgery can be performed at any time, and chemotherapy can be started in the second trimester. Proof of this is the 72 children who have been born under these circumstances in the past 20 years at the Vall d’Hebrón University Hospital. This hospital is a pioneer in Spain thanks to its multidisciplinary program for education and specific follow-up with women who have been diagnosed with a breast tumor during pregnancy.”

Dr. Saura and Dr. Vivancos reported no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Breast cancer has a worse prognosis when diagnosed during pregnancy or postpartum. Methods for early detection are needed, as evidenced every day in the multidisciplinary unit for treating pregnancy-associated breast cancer, which operates within the breast unit at the Vall d’Hebron University Hospital in Barcelona.

The team working in this field is led by Cristina Saura, PhD, who is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO). The results of a study recently published in Cancer Discovery show, for the first time, that breast milk from breast cancer patients contains circulating tumor DNA that can be detected by a liquid biopsy of the milk.

Dr. Saura explained in an interview why they began to pursue this research, which, in one sense, fell into their laps. “In this case, it arose from the concerns of a breast cancer patient who was diagnosed while pregnant with her third daughter. She was actually the one who came up with the idea for the project. She was worried that she had transmitted the tumor through her breast milk to her second daughter while breastfeeding. She had been breastfeeding for a long time and had stretched it out until shortly before she was diagnosed with breast cancer. So she brought us a sample of breast milk that she had stored in her freezer.

“So, thanks to her, that’s where our project started. Though we knew that breast cancer is not transmitted through breast milk, we decided to test the sample and look for markers that could help our research. In the end, when we analyzed the patient’s breast milk, we found DNA with the same mutation that was present in her tumor,” explained Dr. Saura. She noted that the breast milk they analyzed had been frozen for more than a year before the patient’s cancer diagnosis.

In terms of methodology, Ana Vivancos, PhD, head of the VHIO cancer genomics group and also one of the authors of the study, explained that they used two techniques to analyze the breast milk and blood samples: next-generation sequencing and droplet digital polymerase chain reaction. These methods confirmed the presence of ctDNA in the breast milk.
 

High-sensitivity genomic panel

“We were able to detect tumor mutations in milk samples from 13 of the 15 patients with breast cancer who were tested, while circulating tumor DNA was detected in only one of all the blood samples that were collected at the same time,” said Dr. Vivancos. “The samples from the two patients for whom no mutation was detected were discovered to be colostrum that had been collected during the first few hours of lactation.”

As a next step to make this finding practically useful, the research team designed a genomic panel using next-generation sequencing as a potential method for early detection of breast cancer. “We’ve developed a panel that uses hybrid capture chemistry and unique molecular identifiers that ensure better sensitivity during next-generation sequencing. The panel has been calibrated, based on the existing literature, to detect the genes that are most frequently mutated in breast cancer in young women under 45 years old.”

According to Dr. Vivancos, the sensitivity of this panel exceeds 70%. This means that for all the patient samples analyzed using this panel, 7 out of 10 cases are detected with 100% specificity.

“In practice, the panel design allows us to detect mutations in more than 95% of breast cancer cases in women under 45 years old. Therefore, using this panel for early detection of this type of tumor during lactation should contribute to addressing a medical need that, until today, has gone unmet,” noted Dr. Vivancos.

As for this unresolved need, Dr. Saura explained that there is currently no system or tool available to allow early suspicion of breast tumors in pregnant women prior to diagnosis. “That’s exactly the goal of this research: to screen for breast cancer in women who have just given birth. Now, it needs to be validated in a larger group of women in a clinical trial.”
 

More direct contact with tumor cells

In Dr. Saura’s opinion, in Spain, just like taking a small blood sample from newborns in a heel-prick test to rule out metabolic diseases, milk samples could be taken from women who give birth to rule out or diagnose breast cancer.

As to the potential advantages that breast milk liquid biopsy could have over similar techniques like blood liquid biopsy, Dr. Vivancos pointed to the results of her study: “We have seen that breast milk liquid biopsy was positive for the presence of circulating tumor DNA in 87% of cases, whereas blood only revealed the presence of this marker in 8% of cases. This difference indicates that breast milk is a biofluid that is in more direct contact with tumor cells and therefore will be more informative in earlier stages.”

Dr. Saura explained that the data does not lie when it comes to these tumors in pregnant or postpartum women. “In general, they tend to have a worse prognosis because, in most cases, they are diagnosed in advanced stages. Furthermore, it is typically assumed that the physiological changes in the breasts during gestation and lactation, which are considered to be normal, may hide a developing tumor. The fact is that postpartum breast cancer, understood to be the 10 years after delivery, accounts for 40%-45% of breast cancer cases diagnosed before age 45.”

The researchers plan to continue this project. “Our next step to confirm the usefulness of breast milk as a new tool for liquid biopsy for early detection of breast cancer during the postpartum period is to perform this noninvasive test in thousands of women,” said Dr. Saura.
 

Goal: Standardize the test as a screening method

“Based on the results we’ve published, we’re starting a study aimed at collecting breast milk samples from 5,000 healthy women around the world who became pregnant at age 40 or older, or who got pregnant at any age and carry mutations that increase their risk of breast cancer,” Dr. Saura added.

When asked when they expect to have preliminary results from this new study, Dr. Saura stated that it’s not yet possible to say exactly when. “We’re still waiting for funding to continue this project, but we continue performing analyses on a case-by-case basis. Of course, if we detect any abnormalities in these women, we will follow the established protocol to confirm diagnosis and start treatment if necessary.”

When asked whether it is reasonable to expect breast milk liquid biopsy to become normalized as a screening method for women of childbearing age who have a history or risk factors for developing breast cancer, Dr. Vivancos said, “That’s the scenario we see in the future and what we wish to contribute toward by providing scientific evidence to make it a reality.”

“For now, our goal is to validate whether circulating tumor DNA can be detected by breast milk liquid biopsy even before breast cancer can be diagnosed using conventional imaging techniques. If we can validate these preliminary results, we will be able to detect breast cancer early using a noninvasive test like breast milk liquid biopsy,” explained Saura.

Lastly, and in view of the issues that are still unresolved when it comes to the detection and treatment of breast cancer during pregnancy, Dr. Saura highlighted the emotional impact that a diagnosis of pregnancy-related cancer has on women and on those close to them. “But the first thing they need to know is that diagnosis is not necessarily synonymous with termination of the pregnancy. On the contrary, this tumor can be treated during pregnancy, since surgery can be performed at any time, and chemotherapy can be started in the second trimester. Proof of this is the 72 children who have been born under these circumstances in the past 20 years at the Vall d’Hebrón University Hospital. This hospital is a pioneer in Spain thanks to its multidisciplinary program for education and specific follow-up with women who have been diagnosed with a breast tumor during pregnancy.”

Dr. Saura and Dr. Vivancos reported no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Breast cancer has a worse prognosis when diagnosed during pregnancy or postpartum. Methods for early detection are needed, as evidenced every day in the multidisciplinary unit for treating pregnancy-associated breast cancer, which operates within the breast unit at the Vall d’Hebron University Hospital in Barcelona.

The team working in this field is led by Cristina Saura, PhD, who is also head of the Breast Cancer Group at the Vall d’Hebron Institute of Oncology (VHIO). The results of a study recently published in Cancer Discovery show, for the first time, that breast milk from breast cancer patients contains circulating tumor DNA that can be detected by a liquid biopsy of the milk.

Dr. Saura explained in an interview why they began to pursue this research, which, in one sense, fell into their laps. “In this case, it arose from the concerns of a breast cancer patient who was diagnosed while pregnant with her third daughter. She was actually the one who came up with the idea for the project. She was worried that she had transmitted the tumor through her breast milk to her second daughter while breastfeeding. She had been breastfeeding for a long time and had stretched it out until shortly before she was diagnosed with breast cancer. So she brought us a sample of breast milk that she had stored in her freezer.

“So, thanks to her, that’s where our project started. Though we knew that breast cancer is not transmitted through breast milk, we decided to test the sample and look for markers that could help our research. In the end, when we analyzed the patient’s breast milk, we found DNA with the same mutation that was present in her tumor,” explained Dr. Saura. She noted that the breast milk they analyzed had been frozen for more than a year before the patient’s cancer diagnosis.

In terms of methodology, Ana Vivancos, PhD, head of the VHIO cancer genomics group and also one of the authors of the study, explained that they used two techniques to analyze the breast milk and blood samples: next-generation sequencing and droplet digital polymerase chain reaction. These methods confirmed the presence of ctDNA in the breast milk.
 

High-sensitivity genomic panel

“We were able to detect tumor mutations in milk samples from 13 of the 15 patients with breast cancer who were tested, while circulating tumor DNA was detected in only one of all the blood samples that were collected at the same time,” said Dr. Vivancos. “The samples from the two patients for whom no mutation was detected were discovered to be colostrum that had been collected during the first few hours of lactation.”

As a next step to make this finding practically useful, the research team designed a genomic panel using next-generation sequencing as a potential method for early detection of breast cancer. “We’ve developed a panel that uses hybrid capture chemistry and unique molecular identifiers that ensure better sensitivity during next-generation sequencing. The panel has been calibrated, based on the existing literature, to detect the genes that are most frequently mutated in breast cancer in young women under 45 years old.”

According to Dr. Vivancos, the sensitivity of this panel exceeds 70%. This means that for all the patient samples analyzed using this panel, 7 out of 10 cases are detected with 100% specificity.

“In practice, the panel design allows us to detect mutations in more than 95% of breast cancer cases in women under 45 years old. Therefore, using this panel for early detection of this type of tumor during lactation should contribute to addressing a medical need that, until today, has gone unmet,” noted Dr. Vivancos.

As for this unresolved need, Dr. Saura explained that there is currently no system or tool available to allow early suspicion of breast tumors in pregnant women prior to diagnosis. “That’s exactly the goal of this research: to screen for breast cancer in women who have just given birth. Now, it needs to be validated in a larger group of women in a clinical trial.”
 

More direct contact with tumor cells

In Dr. Saura’s opinion, in Spain, just like taking a small blood sample from newborns in a heel-prick test to rule out metabolic diseases, milk samples could be taken from women who give birth to rule out or diagnose breast cancer.

As to the potential advantages that breast milk liquid biopsy could have over similar techniques like blood liquid biopsy, Dr. Vivancos pointed to the results of her study: “We have seen that breast milk liquid biopsy was positive for the presence of circulating tumor DNA in 87% of cases, whereas blood only revealed the presence of this marker in 8% of cases. This difference indicates that breast milk is a biofluid that is in more direct contact with tumor cells and therefore will be more informative in earlier stages.”

Dr. Saura explained that the data does not lie when it comes to these tumors in pregnant or postpartum women. “In general, they tend to have a worse prognosis because, in most cases, they are diagnosed in advanced stages. Furthermore, it is typically assumed that the physiological changes in the breasts during gestation and lactation, which are considered to be normal, may hide a developing tumor. The fact is that postpartum breast cancer, understood to be the 10 years after delivery, accounts for 40%-45% of breast cancer cases diagnosed before age 45.”

The researchers plan to continue this project. “Our next step to confirm the usefulness of breast milk as a new tool for liquid biopsy for early detection of breast cancer during the postpartum period is to perform this noninvasive test in thousands of women,” said Dr. Saura.
 

Goal: Standardize the test as a screening method

“Based on the results we’ve published, we’re starting a study aimed at collecting breast milk samples from 5,000 healthy women around the world who became pregnant at age 40 or older, or who got pregnant at any age and carry mutations that increase their risk of breast cancer,” Dr. Saura added.

When asked when they expect to have preliminary results from this new study, Dr. Saura stated that it’s not yet possible to say exactly when. “We’re still waiting for funding to continue this project, but we continue performing analyses on a case-by-case basis. Of course, if we detect any abnormalities in these women, we will follow the established protocol to confirm diagnosis and start treatment if necessary.”

When asked whether it is reasonable to expect breast milk liquid biopsy to become normalized as a screening method for women of childbearing age who have a history or risk factors for developing breast cancer, Dr. Vivancos said, “That’s the scenario we see in the future and what we wish to contribute toward by providing scientific evidence to make it a reality.”

“For now, our goal is to validate whether circulating tumor DNA can be detected by breast milk liquid biopsy even before breast cancer can be diagnosed using conventional imaging techniques. If we can validate these preliminary results, we will be able to detect breast cancer early using a noninvasive test like breast milk liquid biopsy,” explained Saura.

Lastly, and in view of the issues that are still unresolved when it comes to the detection and treatment of breast cancer during pregnancy, Dr. Saura highlighted the emotional impact that a diagnosis of pregnancy-related cancer has on women and on those close to them. “But the first thing they need to know is that diagnosis is not necessarily synonymous with termination of the pregnancy. On the contrary, this tumor can be treated during pregnancy, since surgery can be performed at any time, and chemotherapy can be started in the second trimester. Proof of this is the 72 children who have been born under these circumstances in the past 20 years at the Vall d’Hebrón University Hospital. This hospital is a pioneer in Spain thanks to its multidisciplinary program for education and specific follow-up with women who have been diagnosed with a breast tumor during pregnancy.”

Dr. Saura and Dr. Vivancos reported no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

TOPLINE:

Overall, making comprehensive dietary changes in line with a Mediterranean diet did not reduce women’s risk for breast cancer recurrence or metastasis. However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.

METHODOLOGY:

• A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
• To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
• All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
• Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
• In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
•  

TAKEAWAY:

• Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
• When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
• The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
•  

IN PRACTICE:

This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.

SOURCE:

The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research. 

LIMITATIONS:

The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.

DISCLOSURES:

The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.

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

TOPLINE:

Overall, making comprehensive dietary changes in line with a Mediterranean diet did not reduce women’s risk for breast cancer recurrence or metastasis. However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.

METHODOLOGY:

• A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
• To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
• All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
• Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
• In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
•  

TAKEAWAY:

• Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
• When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
• The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
•  

IN PRACTICE:

This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.

SOURCE:

The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research. 

LIMITATIONS:

The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.

DISCLOSURES:

The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.

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

TOPLINE:

Overall, making comprehensive dietary changes in line with a Mediterranean diet did not reduce women’s risk for breast cancer recurrence or metastasis. However, women at high risk for recurrence who made the greatest improvements in their diet quality demonstrated a 41% lower risk for recurrence, compared with peers who made the fewest improvements.

METHODOLOGY:

• A growing body of evidence suggests that a better dietary quality may improve survival among patients with breast cancer, but whether diet impacts breast cancer–specific mortality remains controversial.
• To better understand the relationship between diet and breast cancer outcomes, investigators recruited 1,542 women with breast cancer who had undergone surgical resection in the past 5 years and were considered high risk for recurrence.
• All women received general recommendations for cancer prevention, while the intervention group received active support to adhere to a macro–Mediterranean-style diet, which encourages mainly consuming whole grains, legumes, and high-fiber vegetables and discourages eating foods high in saturated and trans fats, processed meats, and foods and beverages high in sugar.
• Diet was assessed at baseline, 1 year, and every few months in subsequent years via food frequency diaries. Compliance with dietary recommendations for the whole cohort was assessed using a dietary index developed for the trial.
• In addition to diet, women in the diet intervention group were encouraged to maintain moderate to intense physical activity – 30 minutes, on average, each day – and received pedometers to track steps, aiming for 10,000 per day.
•  

TAKEAWAY:

• Over 5 years of follow-up, the rate of breast cancer recurrence did not differ between women in the diet intervention group and those in the control group. Overall, 95 of 769 women in the intervention group and 98 of 773 in the control group had a breast cancer recurrence (hazard ratio, 0.99).
• When evaluating outcomes in the entire cohort, looking at everyone’s level of compliance with dietary recommendations, women who adhered the most to the dietary guidelines had a 41% lower recurrence risk compared with women who adhered the least (HR, 0.59).
• The greatest protective effect among women who demonstrated high compliance occurred in those with ER-positive cancers (HR, 0.42) and those with ER-positive cancers who received tamoxifen (HR, 0.30).
•  

IN PRACTICE:

This intervention trial “did not confirm the hypothesis that a comprehensive dietary modification reduces breast cancer recurrence and metastases,” but when looking at compliance to the Mediterranean diet overall, the analysis did find “a significantly better prognosis” for women with the best adherence.

SOURCE:

The study, with first author Franco Berrino, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, was published online in Clinical Cancer Research. 

LIMITATIONS:

The study relied on self-reported dietary data. No dietary instrument was used to estimate nutrient intake and the dietary index developed for the trial remains unvalidated.

DISCLOSURES:

The study was supported by the Italian Department of Health, the Associazione Italiana per la Ricerca sul Cancro, and the Vita e Salute Foundation. The authors reported no relevant financial relationships.

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

The Food and Drug Administration has approved capivasertib (Truqap, AstraZeneca Pharmaceuticals) with fulvestrant for certain previously treated adults with hormone receptor (HR)–positive, human epidermal growth factor receptor (HER2)–negative, locally advanced or metastatic breast cancer.

Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.

Olivier Le Moal/Getty Images

The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.

Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor–based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.

Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.

In the 289 patients with PIK3CA/AKT1/PTEN–altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months versus 3.1 months in the placebo group (hazard ratio, 0.50).

An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% confidence interval, 0.61-1.02), indicating that “the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN alteration,” the FDA explained.

Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.

The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.

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

The Food and Drug Administration has approved capivasertib (Truqap, AstraZeneca Pharmaceuticals) with fulvestrant for certain previously treated adults with hormone receptor (HR)–positive, human epidermal growth factor receptor (HER2)–negative, locally advanced or metastatic breast cancer.

Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.

Olivier Le Moal/Getty Images

The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.

Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor–based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.

Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.

In the 289 patients with PIK3CA/AKT1/PTEN–altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months versus 3.1 months in the placebo group (hazard ratio, 0.50).

An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% confidence interval, 0.61-1.02), indicating that “the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN alteration,” the FDA explained.

Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.

The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.

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

The Food and Drug Administration has approved capivasertib (Truqap, AstraZeneca Pharmaceuticals) with fulvestrant for certain previously treated adults with hormone receptor (HR)–positive, human epidermal growth factor receptor (HER2)–negative, locally advanced or metastatic breast cancer.

Specifically, the first-in-class AKT kinase inhibitor approval is for patients with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, whose metastatic disease progressed on at least one endocrine-based regimen or who experienced recurrence on or within 12 months of completing adjuvant therapy, according to the FDA approval announcement.

Olivier Le Moal/Getty Images

The FDA also approved a companion diagnostic device, the FoundationOne CDx assay, to identify patients who are eligible for treatment with capivasertib.

Approval of capivasertib was based on findings from the randomized, placebo-controlled, phase 3 CAPItello-291 trial, which involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, including 289 whose tumors had PIK3CA/AKT1/PTEN alterations. All had progressed on aromatase inhibitor–based treatment and may have received up to two prior lines of endocrine therapy and up to one line of chemotherapy.

Patients were randomized to either 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle. Patients in both arms received 500 mg intramuscular fulvestrant on cycle 1 days 1 and 15, and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity.

In the 289 patients with PIK3CA/AKT1/PTEN–altered tumors, median progression-free survival (PFS) in the capivasertib arm was 7.3 months versus 3.1 months in the placebo group (hazard ratio, 0.50).

An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/PTEN alteration demonstrated a less notable benefit to the combination (HR, 0.79; 95% confidence interval, 0.61-1.02), indicating that “the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA/AKT1/PTEN alteration,” the FDA explained.

Adverse reactions occurring in at least 20% of patients included decreased lymphocytes, leukocytes, hemoglobin, and neutrophils; increased fasting glucose, creatinine, and triglycerides; and diarrhea, nausea, fatigue, vomiting, and stomatitis.

The recommended capivasertib dose is 400 mg orally twice daily, given about 12 hours apart with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity, according to the prescribing information.

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

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

U.S. government advisers expressed discomfort with Acrotech Biopharma’s 2030 target completion date for a study meant to prove the clinical benefits of two lymphoma drugs that the company has been selling for years.

At a Nov. 16 meeting, the Oncologic Drugs Advisory Committee of the Food and Drug Administration reviewed the reasons for delays in confirmatory trials for pralatrexate (Folotyn) and belinostat (Beleodaq), both now owned by East Windsor, N.J.–based Acrotech. The FDA granted accelerated approval for pralatrexate in 2009 and belinostat in 2014.

“The consensus of the advisory committee is that we have significant concerns about the very prolonged delay and getting these confirmatory studies underway,” said Andy Chen, MD, PhD, of Oregon Health & Science University, Portland, who served as acting ODAC chair for the meeting.

Corporate ownership changes were among the reasons Acrotech cited for the long delays in producing the confirmatory research on pralatrexate and belinostat. Allos Therapeutics won the FDA approval of pralatrexate in 2009. In 2012, Spectrum Pharmaceuticals acquired Acrotech. Spectrum won approval of belinostat in 2014. Acrotech acquired Spectrum in 2019.

The FDA didn’t ask ODAC to take votes on any questions at the meeting. Instead, the FDA sought its expert feedback about how to address the prolonged delays with pralatrexate and belinostat research and, in general, how to promote more timely completion of confirmatory trials for drugs cleared by accelerated approval.

Pralatrexate and belinostat are both used to treat relapsed or refractory peripheral T-cell lymphoma, a rare and aggressive disease affecting about 10,000-15,000 people annually in the United States.

Through the accelerated approval process, the FDA seeks to speed medicines to people with fatal and serious conditions based on promising signs in clinical testing.

The initial pralatrexate and belinostat were based on phase 2, single-arm, monotherapy studies, with about 109 evaluable patients in the key pralatrexate study and 120 evaluable patients in the belinostat study. As is common, these phase 2 tests used measurements of cancer progression, known as the overall response rate.

The FDA then expects companies to show through more extensive testing that medicines cleared with accelerated approvals can deliver significant benefits, such as extending lives. When there are delays in confirmatory trials, patients can be exposed to medicines, often with significant side effects, that are unlikely to benefit them.

For example, the FDA granted an accelerated approval in 2011 for romidepsin for this use for peripheral T-cell lymphoma, the same condition for which pralatrexate and belinostat are used. But in 2021, Bristol-Myers Squibb withdrew the approval for that use of romidepsin when a confirmatory trial failed to meet the primary efficacy endpoint of progression free survival.

At the meeting, Richard Pazdur, MD, who leads oncology medicine at the FDA, urged Acrotech to shorten the time needed to determine whether its medicines deliver significant benefits to patients and thus merit full approval, or whether they too may fall short.

“We’re really in a situation where patients are caught in the middle here,” Dr. Pazdur said. “I feel very bad for that situation and very bad for the patients that they don’t have this information.”
 

‘Dangerous precedent’

The FDA in recent years has stepped up its efforts to get companies to complete their required studies on drugs cleared by accelerated approvals. The FDA has granted a total of 187 accelerated approvals for cancer drugs. Many of these cover new uses of established drugs and others serve to allow the introduction of new medicines.

For more than half of these cases, 96 of 187, the FDA already has learned that it made the right call in allowing early access to medicines. Companies have presented study results that confirmed the benefit of drugs and thus been able to convert accelerated approvals to traditional approvals.

But 27 of the 187 oncology accelerated approvals have been withdrawn. In these cases, subsequent research failed to establish the expected benefits of these cancer drugs.

And in 95 cases, the FDA and companies are still waiting for the results of studies to confirm the expected benefit of drugs granted accelerated approvals. The FDA classifies these as ongoing accelerated approvals. About 85% of these ongoing approvals were granted in the past 5 years, in contrast to 14 years for pralatrexate and 9 for belinostat.

“It sets a dangerous precedent for the other sponsors and drug companies to have such outliers from the same company,” said ODAC member Toni K. Choueiri, MD, of Harvard Medical School and the Dana-Farber Cancer Institute, both in Boston.

The current agreement between the FDA and Acrotech focuses on a phase 3 trial, SPI-BEL-301 as the confirmatory study. Acrotech’s plan is to start with dose optimization studies in part 1 of the trial, with part 2 meant to see if its medicines provide a significant benefit as measured by progression-free survival.

The plan is to compare treatments. One group of patients would get belinostat plus a common cancer regimen known as CHOP, another group would get pralatrexate plus the COP cancer regimen, which is CHOP without doxorubicin, and a third group would get CHOP.

Acrotech’s current time line is for part 1, which began in October, to finish by December 2025. Then the part 2 timeline would run from 2026 to 2030, with interim progression-free survival possible by 2028.

ODAC member Ashley Rosko, MD, a hematologist from Ohio State University, Columbus, asked Acrotech what steps it will take to try to speed recruitment for the study.

“We are going to implement many strategies,” including what’s called digital amplification, replied Ashish Anvekar, president of Acrotech. This will help identify patients and channel them toward participating clinical sites.

Alexander A. Vinks, PhD, PharmD, who served as a temporary member of ODAC for the Nov. 16 meeting, said many clinicians will not be excited about enrolling patients in this kind of large, traditionally designed study.

Dr. Vinks, who is professor emeritus at Cincinnati Children’s Hospital Medical Center and University of Cincinnati, now works with consultant group NDA, a firm that advises companies on developing drugs.

Dr. Vinks advised Acrotech should try “to pin down what is most likely a smaller study that could be simpler, but still give robust, informative data.”

A 49-year-old woman, previously recuperating from COVID-19, was found unconscious at her workplace, setting off a chain of events that would ultimately lead to an unexpected diagnosis.

This case report was published in the New England Journal of Medicine.

Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.

The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.

During the examination, her vital signs were within normal ranges.

The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.

Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.

In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).

Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.

After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.

While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.

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

A 49-year-old woman, previously recuperating from COVID-19, was found unconscious at her workplace, setting off a chain of events that would ultimately lead to an unexpected diagnosis.

This case report was published in the New England Journal of Medicine.

Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.

The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.

During the examination, her vital signs were within normal ranges.

The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.

Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.

In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).

Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.

After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.

While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.

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

A 49-year-old woman, previously recuperating from COVID-19, was found unconscious at her workplace, setting off a chain of events that would ultimately lead to an unexpected diagnosis.

This case report was published in the New England Journal of Medicine.

Noting the patient’s confusion and aphasia, emergency medical services were alerted, and she was taken to the emergency department of Massachusetts General Hospital. Initial examination revealed aphasia and coordination difficulties. However, imaging studies, including CT angiography, showed no signs of stroke or other neurological abnormalities.

The patient’s coworkers had observed that she appeared “unwell.” Her medical history included hypertension, which was managed with amlodipine, and there was no known family history of neurologic disorders.

During the examination, her vital signs were within normal ranges.

The patient’s potassium level of 2.5 mmol/L was noteworthy, indicating hypokalemia. Additionally, the patient presented with anemia and thrombocytopenia. Additional laboratory results unveiled thrombotic thrombocytopenic purpura (TTP), a rare blood disorder characterized by microangiopathic hemolytic anemia. The microscopic examination of a peripheral blood smear confirmed the extent of thrombocytopenia and was particularly notable for the increased number of schistocytes. The patient’s peripheral blood smear revealed five or six schistocytes per high-power field, constituting approximately 5% of the red cells. This significant number of schistocytes aligned with the severity of anemia and thrombocytopenia, confirming the diagnosis of microangiopathic hemolytic anemia.

Acquired TTP is an autoimmune condition driven by antibody-mediated clearance of the plasma enzyme ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif 13). Confirmatory laboratory testing for ADAMTS13 takes 1-3 days; therefore, therapeutic plasma exchange with glucocorticoid therapy and rituximab was initiated, which promptly improved her condition.

In this patient, the ADAMTS13 activity level was severely reduced (< 5%; reference value > 67%), and the inhibitor was present (1.4 inhibitor units; reference value ≤ 0.4).

Rectal cancer was diagnosed in this patient 2 months after the diagnosis of acquired TTP.

After undergoing four weekly infusions of rituximab and a 2-month tapering course of glucocorticoids, the patient experienced a relapse, approximately 6 months following the acquired TTP diagnosis. In response, therapeutic plasma exchange and glucocorticoid therapy were administered. There is a possibility that the underlying cancer played a role in the relapse. To minimize the risk for recurrence, the patient also received a second round of rituximab.

While establishing a clear cause is difficult, acquired TTP often appears to arise in connection with either an immune trigger, such as a viral infection, or immune dysregulation associated with another autoimmune disease or ongoing cancer. In this case, 4 weeks before the acquired TTP diagnosis, the patient had experienced COVID-19, which was likely to be the most probable trigger. However, rectal cancer was also identified in the patient, and whether these conditions are directly linked remains unclear.

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