Popular Weight Loss Drugs Now for Patients With Cancer?

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Changed
Mon, 09/30/2024 - 15:43

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m2 (range, 23-50 kg/m2).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

 

 

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

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Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m2 (range, 23-50 kg/m2).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

 

 

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

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m2 (range, 23-50 kg/m2).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

 

 

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

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FDA approves first gene therapy, betibeglogene autotemcel (Zynteglo), for beta-thalassemia

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Wed, 08/17/2022 - 16:45

 

The U.S. Food and Drug Administration has approved the gene therapy betibeglogene autotemcel (beti-cel) for adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions.

Beta-thalassemia causes a significant reduction of hemoglobin or the absence of hemoglobin altogether, owing to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks. The median age of death is 37 years.

Betibeglogene autotemcel, a one-time gene therapy, represents a potential cure in which functional copies of the mutated gene are inserted into patients’ hematopoietic stem cells via a replication-defective lentivirus.

“Today’s approval is an important advance in the treatment of beta-thalassemia, particularly in individuals who require ongoing red blood cell transfusions,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an FDA press release. “Given the potential health complications associated with this serious disease, this action highlights the FDA’s continued commitment to supporting development of innovative therapies for patients who have limited treatment options.”

The approval was based on phase 3 trials, in which 89% of 41 patients aged 4-34 years who received the therapy maintained normal or near-normal hemoglobin levels and didn’t need transfusions for at least a year. The patients were as young as age 4, maker Bluebird Bio said in a press release.

FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee unanimously recommended approval in June. The gene therapy had been approved in Europe, where it carried a price tag of about $1.8 million, but Bluebird pulled it from the market in 2021 because of problems with reimbursement.

“The decision to discontinue operations in Europe resulted from prolonged negotiations with European payers and challenges to achieving appropriate value recognition and market access,” the company said in a Securities and Exchange Commission filing.

The projected price in the United States is even higher: $2.1 million.

But the Institute for Clinical and Economic Review, an influential Boston-based nonprofit organization that specializes in medical cost-effectiveness analyses, concluded in June that, “given the high annual costs of standard care ... this new treatment meets commonly accepted value thresholds at an anticipated price of $2.1 million,” particularly with Bluebird’s proposal to pay back 80% of the cost if patients need a transfusion within 5 years.

The company is planning an October 2022 launch and estimates the U.S. market for betibeglogene autotemcel to be about 1,500 patients.

Adverse events in studies were “infrequent and consisted primarily of nonserious infusion-related reactions,” such as abdominal pain, hot flush, dyspnea, tachycardia, noncardiac chest pain, and cytopenias, including thrombocytopenia, leukopenia, and neutropenia. One case of thrombocytopenia was considered serious but resolved, according to the company.

Most of the serious adverse events were related to hematopoietic stem cell collection and the busulfan conditioning regimen. Insertional oncogenesis and/or cancer have been reported with Bluebird’s other gene therapy products, but no cases have been associated with betibeglogene autotemcel.

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

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The U.S. Food and Drug Administration has approved the gene therapy betibeglogene autotemcel (beti-cel) for adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions.

Beta-thalassemia causes a significant reduction of hemoglobin or the absence of hemoglobin altogether, owing to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks. The median age of death is 37 years.

Betibeglogene autotemcel, a one-time gene therapy, represents a potential cure in which functional copies of the mutated gene are inserted into patients’ hematopoietic stem cells via a replication-defective lentivirus.

“Today’s approval is an important advance in the treatment of beta-thalassemia, particularly in individuals who require ongoing red blood cell transfusions,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an FDA press release. “Given the potential health complications associated with this serious disease, this action highlights the FDA’s continued commitment to supporting development of innovative therapies for patients who have limited treatment options.”

The approval was based on phase 3 trials, in which 89% of 41 patients aged 4-34 years who received the therapy maintained normal or near-normal hemoglobin levels and didn’t need transfusions for at least a year. The patients were as young as age 4, maker Bluebird Bio said in a press release.

FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee unanimously recommended approval in June. The gene therapy had been approved in Europe, where it carried a price tag of about $1.8 million, but Bluebird pulled it from the market in 2021 because of problems with reimbursement.

“The decision to discontinue operations in Europe resulted from prolonged negotiations with European payers and challenges to achieving appropriate value recognition and market access,” the company said in a Securities and Exchange Commission filing.

The projected price in the United States is even higher: $2.1 million.

But the Institute for Clinical and Economic Review, an influential Boston-based nonprofit organization that specializes in medical cost-effectiveness analyses, concluded in June that, “given the high annual costs of standard care ... this new treatment meets commonly accepted value thresholds at an anticipated price of $2.1 million,” particularly with Bluebird’s proposal to pay back 80% of the cost if patients need a transfusion within 5 years.

The company is planning an October 2022 launch and estimates the U.S. market for betibeglogene autotemcel to be about 1,500 patients.

Adverse events in studies were “infrequent and consisted primarily of nonserious infusion-related reactions,” such as abdominal pain, hot flush, dyspnea, tachycardia, noncardiac chest pain, and cytopenias, including thrombocytopenia, leukopenia, and neutropenia. One case of thrombocytopenia was considered serious but resolved, according to the company.

Most of the serious adverse events were related to hematopoietic stem cell collection and the busulfan conditioning regimen. Insertional oncogenesis and/or cancer have been reported with Bluebird’s other gene therapy products, but no cases have been associated with betibeglogene autotemcel.

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

 

The U.S. Food and Drug Administration has approved the gene therapy betibeglogene autotemcel (beti-cel) for adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions.

Beta-thalassemia causes a significant reduction of hemoglobin or the absence of hemoglobin altogether, owing to mutations in the beta-globin gene. Patients typically require transfusions every 2-5 weeks. The median age of death is 37 years.

Betibeglogene autotemcel, a one-time gene therapy, represents a potential cure in which functional copies of the mutated gene are inserted into patients’ hematopoietic stem cells via a replication-defective lentivirus.

“Today’s approval is an important advance in the treatment of beta-thalassemia, particularly in individuals who require ongoing red blood cell transfusions,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an FDA press release. “Given the potential health complications associated with this serious disease, this action highlights the FDA’s continued commitment to supporting development of innovative therapies for patients who have limited treatment options.”

The approval was based on phase 3 trials, in which 89% of 41 patients aged 4-34 years who received the therapy maintained normal or near-normal hemoglobin levels and didn’t need transfusions for at least a year. The patients were as young as age 4, maker Bluebird Bio said in a press release.

FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee unanimously recommended approval in June. The gene therapy had been approved in Europe, where it carried a price tag of about $1.8 million, but Bluebird pulled it from the market in 2021 because of problems with reimbursement.

“The decision to discontinue operations in Europe resulted from prolonged negotiations with European payers and challenges to achieving appropriate value recognition and market access,” the company said in a Securities and Exchange Commission filing.

The projected price in the United States is even higher: $2.1 million.

But the Institute for Clinical and Economic Review, an influential Boston-based nonprofit organization that specializes in medical cost-effectiveness analyses, concluded in June that, “given the high annual costs of standard care ... this new treatment meets commonly accepted value thresholds at an anticipated price of $2.1 million,” particularly with Bluebird’s proposal to pay back 80% of the cost if patients need a transfusion within 5 years.

The company is planning an October 2022 launch and estimates the U.S. market for betibeglogene autotemcel to be about 1,500 patients.

Adverse events in studies were “infrequent and consisted primarily of nonserious infusion-related reactions,” such as abdominal pain, hot flush, dyspnea, tachycardia, noncardiac chest pain, and cytopenias, including thrombocytopenia, leukopenia, and neutropenia. One case of thrombocytopenia was considered serious but resolved, according to the company.

Most of the serious adverse events were related to hematopoietic stem cell collection and the busulfan conditioning regimen. Insertional oncogenesis and/or cancer have been reported with Bluebird’s other gene therapy products, but no cases have been associated with betibeglogene autotemcel.

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

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Annual PSA screening important for Black men

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Thu, 12/15/2022 - 14:28

 

Annual prostate cancer screening may be particularly important for Black men, new data suggest.

The data come from a review of 45,834 veterans (aged 55-69 years) who had been diagnosed with prostate cancer. About one-third of these men self-identified as non-Hispanic Black, and the rest were White.

During the study period (2004-2017), 2,465 men (5.4%) died of the disease.

The review found that annual prostate-specific antigen (PSA) screening significantly reduced the risk of dying from prostate cancer among Black men but not White men.

The study was published online in JAMA Oncology.

“These results may be biologically plausible because a shorter screening interval may be valuable for detecting aggressive disease, which is more common in Black men,” say investigators, led by University of California, San Diego, radiation oncology resident Michael Sherer, MD.

“Given that Black men are younger at diagnosis and have worse prostate cancer survival compared with White men,” more intensive screening recommendations “may benefit Black patients,” they write.

The study “conclusions are reasonable,” said Christopher Wallis, MD, PhD, a urologic oncologist at Mount Sinai Hospital in Toronto, when asked for comment.

Annual screening may well have “a greater potential to benefit” Black men, he said. “While we would ideally see randomized data supporting this, those data are unlikely to ever be forthcoming. Thus, this study provides a strong rationale to support the recommendations from many guideline panels (including those from the American Urological Association) that Black men, in the context of shared decision-making, may benefit more from PSA-based prostate cancer screening than the population at large,” he added.

Overall, the findings could help inform screening discussions with Black men, the investigators comments. In its most recent guidance, the U.S. Preventive Services Task Force recommends shared decision-making regarding PSA screening for men aged 55-69 years.
 

Similar screening frequency

For their study, the team reviewed Veterans Health Administration data to assess PSA screening patterns – which they categorized as no screening, less than annual screening, or annual screening – in the 5 years leading up to diagnosis.

They then correlated screening behaviors with the subsequent risk of dying from prostate cancer.

Overall, the reduction in risk of prostate cancer–specific mortality (PCSM) associated with screening was similar among Black men (subdistribution hazard ratio, 0.56; P = .001) and White men (sHR, 0.58; P = .001).

However, on multivariable regression, annual screening, in comparison with some screening, was associated with a significant reduction in the risk of dying from prostate cancer only among Black men (sHR, 0.65; P = .02), not among White men (sHR, 0.91; P = .35).

The cumulative incidence of PCSM among Black men was 4.7% with annual screening but 7.3% with only some screening.

Among White men, the cumulative incidence of PCSM with annual screening was 5.9% vs. 6.9% with less than annual screening.

Screening frequency was similar between Black men and White men. Black men were younger on average (61.8 vs. 63.1 years) and had slightly higher PSA levels at diagnosis but were not more likely to have regional or metastatic disease.

No funding was reported for this study. The investigators have disclosed no relevant financial relationships. Dr. Wallis has received personal fees from Janssen Canada.

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

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Annual prostate cancer screening may be particularly important for Black men, new data suggest.

The data come from a review of 45,834 veterans (aged 55-69 years) who had been diagnosed with prostate cancer. About one-third of these men self-identified as non-Hispanic Black, and the rest were White.

During the study period (2004-2017), 2,465 men (5.4%) died of the disease.

The review found that annual prostate-specific antigen (PSA) screening significantly reduced the risk of dying from prostate cancer among Black men but not White men.

The study was published online in JAMA Oncology.

“These results may be biologically plausible because a shorter screening interval may be valuable for detecting aggressive disease, which is more common in Black men,” say investigators, led by University of California, San Diego, radiation oncology resident Michael Sherer, MD.

“Given that Black men are younger at diagnosis and have worse prostate cancer survival compared with White men,” more intensive screening recommendations “may benefit Black patients,” they write.

The study “conclusions are reasonable,” said Christopher Wallis, MD, PhD, a urologic oncologist at Mount Sinai Hospital in Toronto, when asked for comment.

Annual screening may well have “a greater potential to benefit” Black men, he said. “While we would ideally see randomized data supporting this, those data are unlikely to ever be forthcoming. Thus, this study provides a strong rationale to support the recommendations from many guideline panels (including those from the American Urological Association) that Black men, in the context of shared decision-making, may benefit more from PSA-based prostate cancer screening than the population at large,” he added.

Overall, the findings could help inform screening discussions with Black men, the investigators comments. In its most recent guidance, the U.S. Preventive Services Task Force recommends shared decision-making regarding PSA screening for men aged 55-69 years.
 

Similar screening frequency

For their study, the team reviewed Veterans Health Administration data to assess PSA screening patterns – which they categorized as no screening, less than annual screening, or annual screening – in the 5 years leading up to diagnosis.

They then correlated screening behaviors with the subsequent risk of dying from prostate cancer.

Overall, the reduction in risk of prostate cancer–specific mortality (PCSM) associated with screening was similar among Black men (subdistribution hazard ratio, 0.56; P = .001) and White men (sHR, 0.58; P = .001).

However, on multivariable regression, annual screening, in comparison with some screening, was associated with a significant reduction in the risk of dying from prostate cancer only among Black men (sHR, 0.65; P = .02), not among White men (sHR, 0.91; P = .35).

The cumulative incidence of PCSM among Black men was 4.7% with annual screening but 7.3% with only some screening.

Among White men, the cumulative incidence of PCSM with annual screening was 5.9% vs. 6.9% with less than annual screening.

Screening frequency was similar between Black men and White men. Black men were younger on average (61.8 vs. 63.1 years) and had slightly higher PSA levels at diagnosis but were not more likely to have regional or metastatic disease.

No funding was reported for this study. The investigators have disclosed no relevant financial relationships. Dr. Wallis has received personal fees from Janssen Canada.

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

 

Annual prostate cancer screening may be particularly important for Black men, new data suggest.

The data come from a review of 45,834 veterans (aged 55-69 years) who had been diagnosed with prostate cancer. About one-third of these men self-identified as non-Hispanic Black, and the rest were White.

During the study period (2004-2017), 2,465 men (5.4%) died of the disease.

The review found that annual prostate-specific antigen (PSA) screening significantly reduced the risk of dying from prostate cancer among Black men but not White men.

The study was published online in JAMA Oncology.

“These results may be biologically plausible because a shorter screening interval may be valuable for detecting aggressive disease, which is more common in Black men,” say investigators, led by University of California, San Diego, radiation oncology resident Michael Sherer, MD.

“Given that Black men are younger at diagnosis and have worse prostate cancer survival compared with White men,” more intensive screening recommendations “may benefit Black patients,” they write.

The study “conclusions are reasonable,” said Christopher Wallis, MD, PhD, a urologic oncologist at Mount Sinai Hospital in Toronto, when asked for comment.

Annual screening may well have “a greater potential to benefit” Black men, he said. “While we would ideally see randomized data supporting this, those data are unlikely to ever be forthcoming. Thus, this study provides a strong rationale to support the recommendations from many guideline panels (including those from the American Urological Association) that Black men, in the context of shared decision-making, may benefit more from PSA-based prostate cancer screening than the population at large,” he added.

Overall, the findings could help inform screening discussions with Black men, the investigators comments. In its most recent guidance, the U.S. Preventive Services Task Force recommends shared decision-making regarding PSA screening for men aged 55-69 years.
 

Similar screening frequency

For their study, the team reviewed Veterans Health Administration data to assess PSA screening patterns – which they categorized as no screening, less than annual screening, or annual screening – in the 5 years leading up to diagnosis.

They then correlated screening behaviors with the subsequent risk of dying from prostate cancer.

Overall, the reduction in risk of prostate cancer–specific mortality (PCSM) associated with screening was similar among Black men (subdistribution hazard ratio, 0.56; P = .001) and White men (sHR, 0.58; P = .001).

However, on multivariable regression, annual screening, in comparison with some screening, was associated with a significant reduction in the risk of dying from prostate cancer only among Black men (sHR, 0.65; P = .02), not among White men (sHR, 0.91; P = .35).

The cumulative incidence of PCSM among Black men was 4.7% with annual screening but 7.3% with only some screening.

Among White men, the cumulative incidence of PCSM with annual screening was 5.9% vs. 6.9% with less than annual screening.

Screening frequency was similar between Black men and White men. Black men were younger on average (61.8 vs. 63.1 years) and had slightly higher PSA levels at diagnosis but were not more likely to have regional or metastatic disease.

No funding was reported for this study. The investigators have disclosed no relevant financial relationships. Dr. Wallis has received personal fees from Janssen Canada.

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

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FDA approves trastuzumab-deruxtecan for HER2-low breast cancer

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Fri, 12/16/2022 - 10:06

 

The Food and Drug Administration has approved trastuzumab deruxtecan (Enhertu, Daiichi Sankyo/ AstraZeneca) for the treatment of patients with unresectable or metastatic HER2-low breast cancer.

This is the first therapy approved for HER2-low breast cancer, a newly defined subset of HER2-negative breast cancer in which there are some HER2 proteins on the cell surface, but not enough to warrant classification as HER2-positive cancer, the FDA said in a press release.

The indication is for patients who have received prior chemotherapy in the metastatic setting or for patients whose cancer has returned during adjuvant chemotherapy or within 6 months of completing it.

Approval was based on the DESTINY-Breast04 trial, which included 557 patients with unresectable or metastatic HER2-low breast cancer. The trial had two cohorts: 494 hormone receptor–positive (HR+) patients, and 63 hormone receptor–negative (HR–) patients.



Of these patients, 373 were randomly assigned to received trastuzumab deruxtecan every 3 weeks, and 184 were randomly assigned to receive physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel).

Among patients who received trastuzumab deruxtecan, progression-free survival was longer (10.1 months vs. 5.4 months), as was overall survival (23.9 months vs. 17.5 months), compared with those in the chemotherapy group.

“Overall, these results establish HER2-low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” Shanu Modi, MD, said in June at a press conference held during the annual meeting of the American Society of Clinical Oncology, where she presented the results.

The most common adverse reactions in the trial were nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain, and diarrhea. The agent carries a boxed warning regarding the risk of interstitial lung disease and embryo-fetal toxicity.

The targeted agent is not recommended for women who are pregnant.

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

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The Food and Drug Administration has approved trastuzumab deruxtecan (Enhertu, Daiichi Sankyo/ AstraZeneca) for the treatment of patients with unresectable or metastatic HER2-low breast cancer.

This is the first therapy approved for HER2-low breast cancer, a newly defined subset of HER2-negative breast cancer in which there are some HER2 proteins on the cell surface, but not enough to warrant classification as HER2-positive cancer, the FDA said in a press release.

The indication is for patients who have received prior chemotherapy in the metastatic setting or for patients whose cancer has returned during adjuvant chemotherapy or within 6 months of completing it.

Approval was based on the DESTINY-Breast04 trial, which included 557 patients with unresectable or metastatic HER2-low breast cancer. The trial had two cohorts: 494 hormone receptor–positive (HR+) patients, and 63 hormone receptor–negative (HR–) patients.



Of these patients, 373 were randomly assigned to received trastuzumab deruxtecan every 3 weeks, and 184 were randomly assigned to receive physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel).

Among patients who received trastuzumab deruxtecan, progression-free survival was longer (10.1 months vs. 5.4 months), as was overall survival (23.9 months vs. 17.5 months), compared with those in the chemotherapy group.

“Overall, these results establish HER2-low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” Shanu Modi, MD, said in June at a press conference held during the annual meeting of the American Society of Clinical Oncology, where she presented the results.

The most common adverse reactions in the trial were nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain, and diarrhea. The agent carries a boxed warning regarding the risk of interstitial lung disease and embryo-fetal toxicity.

The targeted agent is not recommended for women who are pregnant.

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

 

The Food and Drug Administration has approved trastuzumab deruxtecan (Enhertu, Daiichi Sankyo/ AstraZeneca) for the treatment of patients with unresectable or metastatic HER2-low breast cancer.

This is the first therapy approved for HER2-low breast cancer, a newly defined subset of HER2-negative breast cancer in which there are some HER2 proteins on the cell surface, but not enough to warrant classification as HER2-positive cancer, the FDA said in a press release.

The indication is for patients who have received prior chemotherapy in the metastatic setting or for patients whose cancer has returned during adjuvant chemotherapy or within 6 months of completing it.

Approval was based on the DESTINY-Breast04 trial, which included 557 patients with unresectable or metastatic HER2-low breast cancer. The trial had two cohorts: 494 hormone receptor–positive (HR+) patients, and 63 hormone receptor–negative (HR–) patients.



Of these patients, 373 were randomly assigned to received trastuzumab deruxtecan every 3 weeks, and 184 were randomly assigned to receive physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel).

Among patients who received trastuzumab deruxtecan, progression-free survival was longer (10.1 months vs. 5.4 months), as was overall survival (23.9 months vs. 17.5 months), compared with those in the chemotherapy group.

“Overall, these results establish HER2-low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” Shanu Modi, MD, said in June at a press conference held during the annual meeting of the American Society of Clinical Oncology, where she presented the results.

The most common adverse reactions in the trial were nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain, and diarrhea. The agent carries a boxed warning regarding the risk of interstitial lung disease and embryo-fetal toxicity.

The targeted agent is not recommended for women who are pregnant.

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

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HPV vaccination with Cervarix ‘unmasks’ cervical lesions from non-vax strains

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Tue, 07/05/2022 - 13:58

Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.

However, new evidence suggests that HPV vaccination makes women more susceptible than their nonvaccinated peers to HPV genotypes not covered by the vaccine.

An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.

The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.

After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.

The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.

Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.

The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.

The findings were published online in The Lancet Oncology.

The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.

This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
 

Highlighting a need for caution

The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.

He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.

The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).

There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.

There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.

“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.

These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.

“There might be a little problem if we stop too early,” he said.
 

 

 

Study details

During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.

In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.

There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.

Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.

There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.

Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.

The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.

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

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Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.

However, new evidence suggests that HPV vaccination makes women more susceptible than their nonvaccinated peers to HPV genotypes not covered by the vaccine.

An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.

The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.

After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.

The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.

Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.

The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.

The findings were published online in The Lancet Oncology.

The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.

This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
 

Highlighting a need for caution

The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.

He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.

The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).

There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.

There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.

“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.

These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.

“There might be a little problem if we stop too early,” he said.
 

 

 

Study details

During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.

In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.

There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.

Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.

There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.

Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.

The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.

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

Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.

However, new evidence suggests that HPV vaccination makes women more susceptible than their nonvaccinated peers to HPV genotypes not covered by the vaccine.

An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.

The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.

After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.

The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.

Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.

The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.

The findings were published online in The Lancet Oncology.

The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.

This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
 

Highlighting a need for caution

The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.

He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.

The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).

There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.

There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.

“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.

These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.

“There might be a little problem if we stop too early,” he said.
 

 

 

Study details

During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.

In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.

There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.

Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.

There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.

Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.

The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.

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

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Acetaminophen linked to diminished response to immunotherapy in cancer

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Thu, 06/09/2022 - 08:45

French investigators are warning about using acetaminophen in patients with cancer who are taking immune checkpoint blockers.

The team found a strong association between the use of acetaminophen and a decreased response to immune checkpoint inhibitors in a study of three clinical cohorts involving more than 600 patients with advanced cancer.

Patients who took acetaminophen at the start of immunotherapy – with acetaminophen exposure confirmed by plasma testing – were found to have worse overall survival and progression-free survival than patients who did not take the analgesic. Multivariate analysis confirmed the association independent of other prognostic factors. “It is unlikely that our data are the result of bias or unmeasured confounding,” the authors comment.

The findings “present a compelling case for caution” in using acetaminophen in patients with cancer who are receiving immune checkpoint blockers, senior investigator Antoine Italiano, MD, PhD, a medical oncologist at the University of Bordeaux (France), and colleagues concluded.

The study was presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in Annals of Oncology.

“Patients with advanced cancer taking [acetaminophen] during immunotherapy experience worse clinical outcomes, which suggests that [acetaminophen] decreases T cell–mediated antitumor immunity,” the authors comment.

They also report bench research and blood studies in four healthy volunteers, which showed an up-regulation of immunosuppressive regulatory T cells (Tregs) with acetaminophen, and other findings that together suggest that acetaminophen undermines the antitumor immune processes by which checkpoint inhibitors work.
 

Reconsider acetaminophen pretreatment

After hearing Dr. Italiano present the results at the meeting, a Polish oncologist in the audience said he was concerned that his clinic premedicates with acetaminophen before immune checkpoint blockade and wanted to know if they should stop doing it.

“I don’t think inducing Tregs ... in cancer patients is a good approach. I do a lot of clinical trials,” and “I do not understand why in several cases sponsors required mandatory premedication with acetaminophen. I think ... we should reconsider this approach,” Dr. Italiano said.

There’s precedence for the findings. Acetaminophen – also known as paracetamol – has been shown in some studies to limit immune cell proliferation, T-cell–dependent antibody response, and viral clearance, among other things. After a randomized trial showing blunted responses to vaccines in individuals who were taking acetaminophen, the World Health Organization recommended in 2015 against concurrent use of acetaminophen with vaccines.

Steroids, antibiotics, and proton pump inhibitors have also recently been shown to worsen outcomes with pembrolizumab, noted invited discussant, Margaret Gatti-Mays, MD, a medical oncologist at Ohio State University, Columbus.

“We are starting to understand that ... commonly used medications may have a larger impact on the efficacy and toxicity of immune checkpoint blockade than historically seen with chemotherapy,” she said.

However, she expressed some uncertainty over the French findings, as she was concerned that even the multivariate analysis didn’t completely rule out that acetaminophen users had worse disease to begin with and so would be expected to have worse outcomes.

She was also unsure of how much acetaminophen is too much.

Acetaminophen has a half-life of around 3 hours or less, where the immune checkpoint inhibitors have a half-life of around 20 days or more.

Given that, Dr. Gatti-Mays wondered whether “a single dose of acetaminophen [is] enough to derail the benefit of checkpoint inhibition? Does exposure need to be continuous?”

She allowed that acetaminophen use may turn out to be one more of the many patient-level factors emerging lately – such as chronic stress, diet, body flora, and physiological age, among others – that might help explain why checkpoint inhibition works in only about 20% of eligible patients with cancer.
 

 

 

Study details

Dr. Italiano and his team analyzed plasma samples from 297 participants in the CheckMate 025 trial of nivolumab for renal cancer; 34 participants in the BIP study into actionable molecular alterations in cancer; and 297 participants in the PREMIS immune-related adverse events study. The patients in these last two studies had a variety of cancers and were taking various agents.

All 628 patients were on checkpoint inhibitors. The investigators divided them according to who had acetaminophen or its metabolite acetaminophen glucuronide in their plasma when they started checkpoint inhibition and those who did not.

In CheckMate 025, overall survival was significantly worse among participants who had detectable acetaminophen or its metabolite in plasma (hazard ratio, 0.67; P = .004).

None of the acetaminophen-positive participants in the BIP study responded to checkpoint blockade, compared with almost 30% of those who were negative. Acetaminophen-positive participants also trended toward worse progression-free survival (median, 1.87 vs. 4.72 months) and overall survival (median, 7.87 vs. 16.56 months).

In PREMIS, progression-free survival was a median of 2.63 months in the acetaminophen group versus 5.03 months in negative participants (P = .009); median overall survival was 8.43 months versus 14.93 months, respectively (P < .0001).

A multivariate analysis was performed in PREMIS. Acetaminophen exposure was associated with both progression-free survival (hazard ratio, 1.43; P =.015) and overall survival (HR, 1.78; P =.006) independently of performance status, liver metastases, bone metastases, number of metastases sites, tumor type, number of previous lines of treatment, steroid/antibiotic use, lactate dehydrogenase levels, and other factors.

There was no funding for the work. Dr. Italiano is a consultant for AstraZeneca, Bayer, Chugai, Deciphera, Merck, Parthenon, Roche, and Springworks, He also has grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, MSD, Novartis, Pharmamar, and Roche. Two authors work for Explicyte and one works for Amgen. Dr. Gatti-Mays is a consultant for Seattle Genetics.

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

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French investigators are warning about using acetaminophen in patients with cancer who are taking immune checkpoint blockers.

The team found a strong association between the use of acetaminophen and a decreased response to immune checkpoint inhibitors in a study of three clinical cohorts involving more than 600 patients with advanced cancer.

Patients who took acetaminophen at the start of immunotherapy – with acetaminophen exposure confirmed by plasma testing – were found to have worse overall survival and progression-free survival than patients who did not take the analgesic. Multivariate analysis confirmed the association independent of other prognostic factors. “It is unlikely that our data are the result of bias or unmeasured confounding,” the authors comment.

The findings “present a compelling case for caution” in using acetaminophen in patients with cancer who are receiving immune checkpoint blockers, senior investigator Antoine Italiano, MD, PhD, a medical oncologist at the University of Bordeaux (France), and colleagues concluded.

The study was presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in Annals of Oncology.

“Patients with advanced cancer taking [acetaminophen] during immunotherapy experience worse clinical outcomes, which suggests that [acetaminophen] decreases T cell–mediated antitumor immunity,” the authors comment.

They also report bench research and blood studies in four healthy volunteers, which showed an up-regulation of immunosuppressive regulatory T cells (Tregs) with acetaminophen, and other findings that together suggest that acetaminophen undermines the antitumor immune processes by which checkpoint inhibitors work.
 

Reconsider acetaminophen pretreatment

After hearing Dr. Italiano present the results at the meeting, a Polish oncologist in the audience said he was concerned that his clinic premedicates with acetaminophen before immune checkpoint blockade and wanted to know if they should stop doing it.

“I don’t think inducing Tregs ... in cancer patients is a good approach. I do a lot of clinical trials,” and “I do not understand why in several cases sponsors required mandatory premedication with acetaminophen. I think ... we should reconsider this approach,” Dr. Italiano said.

There’s precedence for the findings. Acetaminophen – also known as paracetamol – has been shown in some studies to limit immune cell proliferation, T-cell–dependent antibody response, and viral clearance, among other things. After a randomized trial showing blunted responses to vaccines in individuals who were taking acetaminophen, the World Health Organization recommended in 2015 against concurrent use of acetaminophen with vaccines.

Steroids, antibiotics, and proton pump inhibitors have also recently been shown to worsen outcomes with pembrolizumab, noted invited discussant, Margaret Gatti-Mays, MD, a medical oncologist at Ohio State University, Columbus.

“We are starting to understand that ... commonly used medications may have a larger impact on the efficacy and toxicity of immune checkpoint blockade than historically seen with chemotherapy,” she said.

However, she expressed some uncertainty over the French findings, as she was concerned that even the multivariate analysis didn’t completely rule out that acetaminophen users had worse disease to begin with and so would be expected to have worse outcomes.

She was also unsure of how much acetaminophen is too much.

Acetaminophen has a half-life of around 3 hours or less, where the immune checkpoint inhibitors have a half-life of around 20 days or more.

Given that, Dr. Gatti-Mays wondered whether “a single dose of acetaminophen [is] enough to derail the benefit of checkpoint inhibition? Does exposure need to be continuous?”

She allowed that acetaminophen use may turn out to be one more of the many patient-level factors emerging lately – such as chronic stress, diet, body flora, and physiological age, among others – that might help explain why checkpoint inhibition works in only about 20% of eligible patients with cancer.
 

 

 

Study details

Dr. Italiano and his team analyzed plasma samples from 297 participants in the CheckMate 025 trial of nivolumab for renal cancer; 34 participants in the BIP study into actionable molecular alterations in cancer; and 297 participants in the PREMIS immune-related adverse events study. The patients in these last two studies had a variety of cancers and were taking various agents.

All 628 patients were on checkpoint inhibitors. The investigators divided them according to who had acetaminophen or its metabolite acetaminophen glucuronide in their plasma when they started checkpoint inhibition and those who did not.

In CheckMate 025, overall survival was significantly worse among participants who had detectable acetaminophen or its metabolite in plasma (hazard ratio, 0.67; P = .004).

None of the acetaminophen-positive participants in the BIP study responded to checkpoint blockade, compared with almost 30% of those who were negative. Acetaminophen-positive participants also trended toward worse progression-free survival (median, 1.87 vs. 4.72 months) and overall survival (median, 7.87 vs. 16.56 months).

In PREMIS, progression-free survival was a median of 2.63 months in the acetaminophen group versus 5.03 months in negative participants (P = .009); median overall survival was 8.43 months versus 14.93 months, respectively (P < .0001).

A multivariate analysis was performed in PREMIS. Acetaminophen exposure was associated with both progression-free survival (hazard ratio, 1.43; P =.015) and overall survival (HR, 1.78; P =.006) independently of performance status, liver metastases, bone metastases, number of metastases sites, tumor type, number of previous lines of treatment, steroid/antibiotic use, lactate dehydrogenase levels, and other factors.

There was no funding for the work. Dr. Italiano is a consultant for AstraZeneca, Bayer, Chugai, Deciphera, Merck, Parthenon, Roche, and Springworks, He also has grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, MSD, Novartis, Pharmamar, and Roche. Two authors work for Explicyte and one works for Amgen. Dr. Gatti-Mays is a consultant for Seattle Genetics.

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

French investigators are warning about using acetaminophen in patients with cancer who are taking immune checkpoint blockers.

The team found a strong association between the use of acetaminophen and a decreased response to immune checkpoint inhibitors in a study of three clinical cohorts involving more than 600 patients with advanced cancer.

Patients who took acetaminophen at the start of immunotherapy – with acetaminophen exposure confirmed by plasma testing – were found to have worse overall survival and progression-free survival than patients who did not take the analgesic. Multivariate analysis confirmed the association independent of other prognostic factors. “It is unlikely that our data are the result of bias or unmeasured confounding,” the authors comment.

The findings “present a compelling case for caution” in using acetaminophen in patients with cancer who are receiving immune checkpoint blockers, senior investigator Antoine Italiano, MD, PhD, a medical oncologist at the University of Bordeaux (France), and colleagues concluded.

The study was presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in Annals of Oncology.

“Patients with advanced cancer taking [acetaminophen] during immunotherapy experience worse clinical outcomes, which suggests that [acetaminophen] decreases T cell–mediated antitumor immunity,” the authors comment.

They also report bench research and blood studies in four healthy volunteers, which showed an up-regulation of immunosuppressive regulatory T cells (Tregs) with acetaminophen, and other findings that together suggest that acetaminophen undermines the antitumor immune processes by which checkpoint inhibitors work.
 

Reconsider acetaminophen pretreatment

After hearing Dr. Italiano present the results at the meeting, a Polish oncologist in the audience said he was concerned that his clinic premedicates with acetaminophen before immune checkpoint blockade and wanted to know if they should stop doing it.

“I don’t think inducing Tregs ... in cancer patients is a good approach. I do a lot of clinical trials,” and “I do not understand why in several cases sponsors required mandatory premedication with acetaminophen. I think ... we should reconsider this approach,” Dr. Italiano said.

There’s precedence for the findings. Acetaminophen – also known as paracetamol – has been shown in some studies to limit immune cell proliferation, T-cell–dependent antibody response, and viral clearance, among other things. After a randomized trial showing blunted responses to vaccines in individuals who were taking acetaminophen, the World Health Organization recommended in 2015 against concurrent use of acetaminophen with vaccines.

Steroids, antibiotics, and proton pump inhibitors have also recently been shown to worsen outcomes with pembrolizumab, noted invited discussant, Margaret Gatti-Mays, MD, a medical oncologist at Ohio State University, Columbus.

“We are starting to understand that ... commonly used medications may have a larger impact on the efficacy and toxicity of immune checkpoint blockade than historically seen with chemotherapy,” she said.

However, she expressed some uncertainty over the French findings, as she was concerned that even the multivariate analysis didn’t completely rule out that acetaminophen users had worse disease to begin with and so would be expected to have worse outcomes.

She was also unsure of how much acetaminophen is too much.

Acetaminophen has a half-life of around 3 hours or less, where the immune checkpoint inhibitors have a half-life of around 20 days or more.

Given that, Dr. Gatti-Mays wondered whether “a single dose of acetaminophen [is] enough to derail the benefit of checkpoint inhibition? Does exposure need to be continuous?”

She allowed that acetaminophen use may turn out to be one more of the many patient-level factors emerging lately – such as chronic stress, diet, body flora, and physiological age, among others – that might help explain why checkpoint inhibition works in only about 20% of eligible patients with cancer.
 

 

 

Study details

Dr. Italiano and his team analyzed plasma samples from 297 participants in the CheckMate 025 trial of nivolumab for renal cancer; 34 participants in the BIP study into actionable molecular alterations in cancer; and 297 participants in the PREMIS immune-related adverse events study. The patients in these last two studies had a variety of cancers and were taking various agents.

All 628 patients were on checkpoint inhibitors. The investigators divided them according to who had acetaminophen or its metabolite acetaminophen glucuronide in their plasma when they started checkpoint inhibition and those who did not.

In CheckMate 025, overall survival was significantly worse among participants who had detectable acetaminophen or its metabolite in plasma (hazard ratio, 0.67; P = .004).

None of the acetaminophen-positive participants in the BIP study responded to checkpoint blockade, compared with almost 30% of those who were negative. Acetaminophen-positive participants also trended toward worse progression-free survival (median, 1.87 vs. 4.72 months) and overall survival (median, 7.87 vs. 16.56 months).

In PREMIS, progression-free survival was a median of 2.63 months in the acetaminophen group versus 5.03 months in negative participants (P = .009); median overall survival was 8.43 months versus 14.93 months, respectively (P < .0001).

A multivariate analysis was performed in PREMIS. Acetaminophen exposure was associated with both progression-free survival (hazard ratio, 1.43; P =.015) and overall survival (HR, 1.78; P =.006) independently of performance status, liver metastases, bone metastases, number of metastases sites, tumor type, number of previous lines of treatment, steroid/antibiotic use, lactate dehydrogenase levels, and other factors.

There was no funding for the work. Dr. Italiano is a consultant for AstraZeneca, Bayer, Chugai, Deciphera, Merck, Parthenon, Roche, and Springworks, He also has grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, MSD, Novartis, Pharmamar, and Roche. Two authors work for Explicyte and one works for Amgen. Dr. Gatti-Mays is a consultant for Seattle Genetics.

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

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Debate: Should biologics be used for milder cases of psoriasis?

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Changed
Tue, 02/07/2023 - 16:46

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

Dr. Kenneth Brian Gordon

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.



Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Dr. Richard Langley

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

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The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

Dr. Kenneth Brian Gordon

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.



Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Dr. Richard Langley

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

The remarkable efficacy of biologics for moderate to severe psoriasis has led some to ask if biologics should be used for milder cases.

Dr. Kenneth Brian Gordon

The issue was tackled in a debate at the American Academy of Dermatology Virtual Meeting Experience.

Taking the con side, Kenneth Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee, argued that, with the high cost of biologics, availability of many alternatives, and other issues, “we should just say no. ... There is no good reason that we need to expand the use of biologics in patients with limited disease.”

On the pro side, Richard Langley, MD, professor of dermatology at Dalhousie University Halifax, N.S, argued for a nuanced approach. He noted that patients with smaller patches of disease can be just as miserable as patients who hit traditional benchmarks of increased severity, such as high body surface area involvement – especially if those small areas are in sensitive locations like the scalp, palms, or genitals.

The decision to use a biologic should hinge on how badly patients and their quality of life are affected, not on “some artificial and limiting definition” of severity, Dr. Langley said.

Dr. Gordon didn’t disagree, noting that current use criteria include objective measures as well as disease in sensitive areas and failure of alternative treatments.



Rather, he was concerned about “expanding the definition of who is eligible beyond these criteria ... to chase every last bit of” disease. “I don’t think we have” a good rationale for that approach, he said.

Cost is the most important issue, Dr. Gordon said.

With more biologics on the way and prices continuing to go up, “there is going to a be a huge challenge to our use of these expensive medicines over the next few years” from payers. “It is important that we use them smartly in order to make sure we are able to use them for people with severe disease” who really need them. If “we start using biologics for all our patients with psoriasis,” it will be a “cost disaster,” Dr. Gordon said.

In addition, topicals and home phototherapy can be effective as long as patients adhere to them, as can alternative systemic agents, such as methotrexate and apremilast.

Often with biologics, “the issue is mainly convenience” rather than a fundamental problem with the alternatives, and despite the good safety record in trials, “chasing the last bit” of psoriasis with a biologic “is not necessarily” without risk for the patient, Dr. Gordon said.

Dr. Richard Langley

Still, there can be a “pretty significant disconnect” between how patients perceive their psoriasis and “what physicians are thinking and prescribing” for it based on objective measures, Dr. Langley noted. Sometimes patients who have limited disease but are in significant distress aren’t even receiving treatment or are only given another cream to add to their collection of ones that haven’t worked.

One problem with traditional severity classifications is that they don’t generally take patients’ subjective experience into account, he added. There’s also been a lack of standardization to the point that dermatologists, researchers, and payers can sometimes disagree over severity in a given patient.

There’s movement toward better incorporation of patient experience into severity considerations, but for now at least, a designation of mild psoriasis can underestimate the true severity of disease, Dr. Langley said.

Dr. Gordon and Dr. Langley reported receiving honoraria and/or research support from many pharmaceutical companies, including AbbVie, Pfizer, and Lilly.

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

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Clearance rates higher with bimekizumab vs. secukinumab in phase 3 psoriasis study

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Wed, 04/28/2021 - 10:15

Secukinumab is the latest adult plaque psoriasis treatment to be bested by a newcomer, the interleukin 17A and 17F blocker bimekizumab.

Rates of complete clearance were substantially higher with bimekizumab in a phase 3 trial with 743 patients with moderate-to-severe plaque psoriasis, but oral candidiasis (oral thrush) again emerged as a particular issue with the agent.

Clinical improvements seen with bimekizumab have exceeded those with two standard options for adult plaque psoriasis — the tumor necrosis factor blocker adalimumab and the interleukin (IL) 12/23 inhibitor ustekinumab

 — in phase 3 trials from manufacturer UCB Pharma, and it›s under review for the indication by the U.S. Food and Drug Administration and the European Medicines Agency.

The biologic is also being evaluated in phase 3 trials for treating psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa.

Results of the trial comparing bimekizumab to secukinumab, dubbed BE RADIANT, were presented at the American Academy of Dermatology Virtual Meeting Experience and published online concurrently April 23 in the New England Journal of Medicine.

The results “suggest that inhibition of both interleukin-17A and interleukin-17F with bimekizumab may provide greater clinical benefit for patients with moderate-to-severe plaque psoriasis than inhibition of interleukin-17A alone,” as with secukinumab, said the investigators, led by Kristian Reich, MD,  professor of dermatology at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.

The trial randomly assigned 373 adults to bimekizumab 320 mg every 4 weeks to week 16, then rerandomized them to maintenance dosing either every 4 weeks or every 8 weeks to week 48; another 370 adults were randomly assigned to secukinumab 300 mg weekly for the first 4 weeks, then every 4 weeks to week 48. Baseline Psoriasis Area and Severity Index (PASI) scores were about 20 points in both treatment groups.

At the 1-month point, 71% in the bimekizumab group, vs 47.3% on secukinumab, had a 75% or greater reduction from their baseline PASI score. At 4 months, 61.7% of those on bimekizumab but 48.9% in the secukinumab group had complete clearance with a PASI score of 100.

At 48 weeks, 67% of those on bimekizumab had a PASI 100 response — which was numerically similar between the two bimekizumab dosing regimens after week 16 — vs 46.2% of the secukinumab group (P for all < .001).

The incidence of serious adverse events was just under 6% in both groups, with adverse events leading to discontinuation in 3.5% of bimekizumab and 2.7% of secukinumab subjects. The rate of serious infections was similar in both groups.

However, as in past trials, oral candidiasis was an issue, occurring in 19.3% of bimekizumab subjects vs 3% on secukinumab. Half of the 72 bimekizumab cases were classified as mild, and all but two of the rest as moderate. Over 40% of affected subjects reported more than one case, but none led to treatment discontinuation.

More than 85% of oral candidiasis cases in the study were treated with antifungal therapy and resolved during the trial. Inflammatory bowel disease is a concern with IL-17 blockade, but this hasn’t emerged as a particular issue with bimekizumab. There was one case each of ulcerative colitis in both the bimekizumab and secukinumab groups, and just one case of ulcerative colitis in three previous phase 3 bimekizumab trials, according to the investigators.

Among the trial limitations: Patients who had been on bimekizumab or secukinumab previously were excluded, as were patients who had no response to an IL-17 biologic or more than one biologic agent of any other class within the previous 12 weeks. The limitations could reduce generalizability, the investigators said.

Patients in the trial were about 45 years old, on average, and about two thirds were men; over 90% were White.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Reich who reported grants and personal fees from companies including UCB Pharma. The full list of disclosures can be found with the New England Journal of Medicine article.

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

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Secukinumab is the latest adult plaque psoriasis treatment to be bested by a newcomer, the interleukin 17A and 17F blocker bimekizumab.

Rates of complete clearance were substantially higher with bimekizumab in a phase 3 trial with 743 patients with moderate-to-severe plaque psoriasis, but oral candidiasis (oral thrush) again emerged as a particular issue with the agent.

Clinical improvements seen with bimekizumab have exceeded those with two standard options for adult plaque psoriasis — the tumor necrosis factor blocker adalimumab and the interleukin (IL) 12/23 inhibitor ustekinumab

 — in phase 3 trials from manufacturer UCB Pharma, and it›s under review for the indication by the U.S. Food and Drug Administration and the European Medicines Agency.

The biologic is also being evaluated in phase 3 trials for treating psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa.

Results of the trial comparing bimekizumab to secukinumab, dubbed BE RADIANT, were presented at the American Academy of Dermatology Virtual Meeting Experience and published online concurrently April 23 in the New England Journal of Medicine.

The results “suggest that inhibition of both interleukin-17A and interleukin-17F with bimekizumab may provide greater clinical benefit for patients with moderate-to-severe plaque psoriasis than inhibition of interleukin-17A alone,” as with secukinumab, said the investigators, led by Kristian Reich, MD,  professor of dermatology at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.

The trial randomly assigned 373 adults to bimekizumab 320 mg every 4 weeks to week 16, then rerandomized them to maintenance dosing either every 4 weeks or every 8 weeks to week 48; another 370 adults were randomly assigned to secukinumab 300 mg weekly for the first 4 weeks, then every 4 weeks to week 48. Baseline Psoriasis Area and Severity Index (PASI) scores were about 20 points in both treatment groups.

At the 1-month point, 71% in the bimekizumab group, vs 47.3% on secukinumab, had a 75% or greater reduction from their baseline PASI score. At 4 months, 61.7% of those on bimekizumab but 48.9% in the secukinumab group had complete clearance with a PASI score of 100.

At 48 weeks, 67% of those on bimekizumab had a PASI 100 response — which was numerically similar between the two bimekizumab dosing regimens after week 16 — vs 46.2% of the secukinumab group (P for all < .001).

The incidence of serious adverse events was just under 6% in both groups, with adverse events leading to discontinuation in 3.5% of bimekizumab and 2.7% of secukinumab subjects. The rate of serious infections was similar in both groups.

However, as in past trials, oral candidiasis was an issue, occurring in 19.3% of bimekizumab subjects vs 3% on secukinumab. Half of the 72 bimekizumab cases were classified as mild, and all but two of the rest as moderate. Over 40% of affected subjects reported more than one case, but none led to treatment discontinuation.

More than 85% of oral candidiasis cases in the study were treated with antifungal therapy and resolved during the trial. Inflammatory bowel disease is a concern with IL-17 blockade, but this hasn’t emerged as a particular issue with bimekizumab. There was one case each of ulcerative colitis in both the bimekizumab and secukinumab groups, and just one case of ulcerative colitis in three previous phase 3 bimekizumab trials, according to the investigators.

Among the trial limitations: Patients who had been on bimekizumab or secukinumab previously were excluded, as were patients who had no response to an IL-17 biologic or more than one biologic agent of any other class within the previous 12 weeks. The limitations could reduce generalizability, the investigators said.

Patients in the trial were about 45 years old, on average, and about two thirds were men; over 90% were White.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Reich who reported grants and personal fees from companies including UCB Pharma. The full list of disclosures can be found with the New England Journal of Medicine article.

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

Secukinumab is the latest adult plaque psoriasis treatment to be bested by a newcomer, the interleukin 17A and 17F blocker bimekizumab.

Rates of complete clearance were substantially higher with bimekizumab in a phase 3 trial with 743 patients with moderate-to-severe plaque psoriasis, but oral candidiasis (oral thrush) again emerged as a particular issue with the agent.

Clinical improvements seen with bimekizumab have exceeded those with two standard options for adult plaque psoriasis — the tumor necrosis factor blocker adalimumab and the interleukin (IL) 12/23 inhibitor ustekinumab

 — in phase 3 trials from manufacturer UCB Pharma, and it›s under review for the indication by the U.S. Food and Drug Administration and the European Medicines Agency.

The biologic is also being evaluated in phase 3 trials for treating psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa.

Results of the trial comparing bimekizumab to secukinumab, dubbed BE RADIANT, were presented at the American Academy of Dermatology Virtual Meeting Experience and published online concurrently April 23 in the New England Journal of Medicine.

The results “suggest that inhibition of both interleukin-17A and interleukin-17F with bimekizumab may provide greater clinical benefit for patients with moderate-to-severe plaque psoriasis than inhibition of interleukin-17A alone,” as with secukinumab, said the investigators, led by Kristian Reich, MD,  professor of dermatology at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.

The trial randomly assigned 373 adults to bimekizumab 320 mg every 4 weeks to week 16, then rerandomized them to maintenance dosing either every 4 weeks or every 8 weeks to week 48; another 370 adults were randomly assigned to secukinumab 300 mg weekly for the first 4 weeks, then every 4 weeks to week 48. Baseline Psoriasis Area and Severity Index (PASI) scores were about 20 points in both treatment groups.

At the 1-month point, 71% in the bimekizumab group, vs 47.3% on secukinumab, had a 75% or greater reduction from their baseline PASI score. At 4 months, 61.7% of those on bimekizumab but 48.9% in the secukinumab group had complete clearance with a PASI score of 100.

At 48 weeks, 67% of those on bimekizumab had a PASI 100 response — which was numerically similar between the two bimekizumab dosing regimens after week 16 — vs 46.2% of the secukinumab group (P for all < .001).

The incidence of serious adverse events was just under 6% in both groups, with adverse events leading to discontinuation in 3.5% of bimekizumab and 2.7% of secukinumab subjects. The rate of serious infections was similar in both groups.

However, as in past trials, oral candidiasis was an issue, occurring in 19.3% of bimekizumab subjects vs 3% on secukinumab. Half of the 72 bimekizumab cases were classified as mild, and all but two of the rest as moderate. Over 40% of affected subjects reported more than one case, but none led to treatment discontinuation.

More than 85% of oral candidiasis cases in the study were treated with antifungal therapy and resolved during the trial. Inflammatory bowel disease is a concern with IL-17 blockade, but this hasn’t emerged as a particular issue with bimekizumab. There was one case each of ulcerative colitis in both the bimekizumab and secukinumab groups, and just one case of ulcerative colitis in three previous phase 3 bimekizumab trials, according to the investigators.

Among the trial limitations: Patients who had been on bimekizumab or secukinumab previously were excluded, as were patients who had no response to an IL-17 biologic or more than one biologic agent of any other class within the previous 12 weeks. The limitations could reduce generalizability, the investigators said.

Patients in the trial were about 45 years old, on average, and about two thirds were men; over 90% were White.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Reich who reported grants and personal fees from companies including UCB Pharma. The full list of disclosures can be found with the New England Journal of Medicine article.

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

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Bimekizumab tops adalimumab for plaque psoriasis

Article Type
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Sat, 04/24/2021 - 09:20

Bimekizumab bested adalimumab for moderate to severe plaque psoriasis in a phase 3 trial of adults from the agent’s maker UCB Pharma.

The interleukin-17A and 17F blocker has also racked up significant wins against ustekinumab and secukinumab, other standard biologic options for adults with moderate to severe plaque psoriasis, and is currently under review for the indication by the U.S. Food and Drug Administration and European Medicines Agency.

In the adalimumab trial, dubbed BE SURE, bimekizumab had higher clinical response rates than the tumor necrosis factor (TNF) blocker over the 24-week head-to-head phase of the 478-patient trial, with substantial improvements in both Psoriasis Area and Severity Index (PASI) 90 response and Investigator’s Global Assessment (IGA) scores of 0 or 1, which signifies clear or almost clear skin.

The results were published in the New England Journal of Medicine and scheduled to be presented at the American Academy of Dermatology Virtual Meeting Experience on April 24.

“The data look good,” said psoriasis specialist Steven Feldman, MD, PhD, professor of dermatology at Wake Forest School of Medicine in Winston-Salem, N.C., when asked for comment.

Bimekizumab “appears more effective than current options. The big question is safety. The 10%-20% rate of oral candidiasis is much higher than other treatments but should be entirely manageable, as long as there are no unknown worse candida issues.” In addition, that there were no cases of inflammatory bowel disease in BE SURE “is very encouraging, as that is one of the limitations for existing IL-17 blockers,” he said.

The trial was launched after previous reports suggested that IL-17A inhibition may be better than TNF blockade in controlling psoriasis, said investigators led by Richard Warren, MBChB, PhD, a dermatology professor at the University of Manchester (England).

Patients were assigned evenly to one of three regimens: subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at 320 mg every 4 weeks for 16 weeks, then every 8 weeks out to 56 weeks; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56.

At week 16, 86.2% of those in the bimekizumab group but just 47.2% in the adalimumab group had a PASI 90 response (P < .001), and 85.3% of the bimekizumab versus 57.2% in the adalimumab group had an IGA score of 0 or 1 (P < .001).

About 52% of the adalimumab group had a PASI 90 response at week 24, when they were switched to bimekizumab. By week 56, their PASI 90 response rate rose to 81.8%. Skin clearance was maintained through week 56 whether subjects were dosed every 4 or every 8 weeks with the interleukin blocker.

The incidence of oral candidiasis (9.5%-17.4% vs. 0% with adalimumab alone) was similar to other trials and likely because of the short circuiting of interleukin-17, which plays a role protecting against candida. Most cases were mild to moderate.

The increased risk of oral thrush with bimekizumab “may not be particularly clinically meaningful, especially if” it can be managed by an occasional fluconazole pill. It’s “reassuring … if that’s the biggest problem with the drug, or we may wonder if, in real life use, more severe, perhaps esophageal or systemic fungal infection may be observed,” Dr. Feldman said in a recent editorial.

“Not knowing the future may make some physicians reticent about using the drug when other options are available, at least until data are available on much larger numbers of exposed patients treated for longer periods of time,” he and his colleague William Huang, MD, also a dermatologist at Wake Forest, said.

One of the limits of the trial was that the head-to-head portion was only 24 weeks, “which was too brief for a comparison of safety between bimekizumab and adalimumab in a lifelong disease,” the investigators noted.

The mean age of the patients was 44.9 years, and the mean baseline PASI score was 19.8.

Although the initial dose of adalimumab in the study was 40 mg, labeling recommends an initial dose of 80 mg for the TNF blocker.

Bimekizumab is also being evaluated in phase 3 trials for psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa, according to UCB Pharma.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Dr. Warren who reported grants and personal fees from the company. Dr. Feldman reported receiving research, speaking, and/or consulting support from UCB Pharma and other companies.

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

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Bimekizumab bested adalimumab for moderate to severe plaque psoriasis in a phase 3 trial of adults from the agent’s maker UCB Pharma.

The interleukin-17A and 17F blocker has also racked up significant wins against ustekinumab and secukinumab, other standard biologic options for adults with moderate to severe plaque psoriasis, and is currently under review for the indication by the U.S. Food and Drug Administration and European Medicines Agency.

In the adalimumab trial, dubbed BE SURE, bimekizumab had higher clinical response rates than the tumor necrosis factor (TNF) blocker over the 24-week head-to-head phase of the 478-patient trial, with substantial improvements in both Psoriasis Area and Severity Index (PASI) 90 response and Investigator’s Global Assessment (IGA) scores of 0 or 1, which signifies clear or almost clear skin.

The results were published in the New England Journal of Medicine and scheduled to be presented at the American Academy of Dermatology Virtual Meeting Experience on April 24.

“The data look good,” said psoriasis specialist Steven Feldman, MD, PhD, professor of dermatology at Wake Forest School of Medicine in Winston-Salem, N.C., when asked for comment.

Bimekizumab “appears more effective than current options. The big question is safety. The 10%-20% rate of oral candidiasis is much higher than other treatments but should be entirely manageable, as long as there are no unknown worse candida issues.” In addition, that there were no cases of inflammatory bowel disease in BE SURE “is very encouraging, as that is one of the limitations for existing IL-17 blockers,” he said.

The trial was launched after previous reports suggested that IL-17A inhibition may be better than TNF blockade in controlling psoriasis, said investigators led by Richard Warren, MBChB, PhD, a dermatology professor at the University of Manchester (England).

Patients were assigned evenly to one of three regimens: subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at 320 mg every 4 weeks for 16 weeks, then every 8 weeks out to 56 weeks; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56.

At week 16, 86.2% of those in the bimekizumab group but just 47.2% in the adalimumab group had a PASI 90 response (P < .001), and 85.3% of the bimekizumab versus 57.2% in the adalimumab group had an IGA score of 0 or 1 (P < .001).

About 52% of the adalimumab group had a PASI 90 response at week 24, when they were switched to bimekizumab. By week 56, their PASI 90 response rate rose to 81.8%. Skin clearance was maintained through week 56 whether subjects were dosed every 4 or every 8 weeks with the interleukin blocker.

The incidence of oral candidiasis (9.5%-17.4% vs. 0% with adalimumab alone) was similar to other trials and likely because of the short circuiting of interleukin-17, which plays a role protecting against candida. Most cases were mild to moderate.

The increased risk of oral thrush with bimekizumab “may not be particularly clinically meaningful, especially if” it can be managed by an occasional fluconazole pill. It’s “reassuring … if that’s the biggest problem with the drug, or we may wonder if, in real life use, more severe, perhaps esophageal or systemic fungal infection may be observed,” Dr. Feldman said in a recent editorial.

“Not knowing the future may make some physicians reticent about using the drug when other options are available, at least until data are available on much larger numbers of exposed patients treated for longer periods of time,” he and his colleague William Huang, MD, also a dermatologist at Wake Forest, said.

One of the limits of the trial was that the head-to-head portion was only 24 weeks, “which was too brief for a comparison of safety between bimekizumab and adalimumab in a lifelong disease,” the investigators noted.

The mean age of the patients was 44.9 years, and the mean baseline PASI score was 19.8.

Although the initial dose of adalimumab in the study was 40 mg, labeling recommends an initial dose of 80 mg for the TNF blocker.

Bimekizumab is also being evaluated in phase 3 trials for psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa, according to UCB Pharma.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Dr. Warren who reported grants and personal fees from the company. Dr. Feldman reported receiving research, speaking, and/or consulting support from UCB Pharma and other companies.

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

Bimekizumab bested adalimumab for moderate to severe plaque psoriasis in a phase 3 trial of adults from the agent’s maker UCB Pharma.

The interleukin-17A and 17F blocker has also racked up significant wins against ustekinumab and secukinumab, other standard biologic options for adults with moderate to severe plaque psoriasis, and is currently under review for the indication by the U.S. Food and Drug Administration and European Medicines Agency.

In the adalimumab trial, dubbed BE SURE, bimekizumab had higher clinical response rates than the tumor necrosis factor (TNF) blocker over the 24-week head-to-head phase of the 478-patient trial, with substantial improvements in both Psoriasis Area and Severity Index (PASI) 90 response and Investigator’s Global Assessment (IGA) scores of 0 or 1, which signifies clear or almost clear skin.

The results were published in the New England Journal of Medicine and scheduled to be presented at the American Academy of Dermatology Virtual Meeting Experience on April 24.

“The data look good,” said psoriasis specialist Steven Feldman, MD, PhD, professor of dermatology at Wake Forest School of Medicine in Winston-Salem, N.C., when asked for comment.

Bimekizumab “appears more effective than current options. The big question is safety. The 10%-20% rate of oral candidiasis is much higher than other treatments but should be entirely manageable, as long as there are no unknown worse candida issues.” In addition, that there were no cases of inflammatory bowel disease in BE SURE “is very encouraging, as that is one of the limitations for existing IL-17 blockers,” he said.

The trial was launched after previous reports suggested that IL-17A inhibition may be better than TNF blockade in controlling psoriasis, said investigators led by Richard Warren, MBChB, PhD, a dermatology professor at the University of Manchester (England).

Patients were assigned evenly to one of three regimens: subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at 320 mg every 4 weeks for 16 weeks, then every 8 weeks out to 56 weeks; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56.

At week 16, 86.2% of those in the bimekizumab group but just 47.2% in the adalimumab group had a PASI 90 response (P < .001), and 85.3% of the bimekizumab versus 57.2% in the adalimumab group had an IGA score of 0 or 1 (P < .001).

About 52% of the adalimumab group had a PASI 90 response at week 24, when they were switched to bimekizumab. By week 56, their PASI 90 response rate rose to 81.8%. Skin clearance was maintained through week 56 whether subjects were dosed every 4 or every 8 weeks with the interleukin blocker.

The incidence of oral candidiasis (9.5%-17.4% vs. 0% with adalimumab alone) was similar to other trials and likely because of the short circuiting of interleukin-17, which plays a role protecting against candida. Most cases were mild to moderate.

The increased risk of oral thrush with bimekizumab “may not be particularly clinically meaningful, especially if” it can be managed by an occasional fluconazole pill. It’s “reassuring … if that’s the biggest problem with the drug, or we may wonder if, in real life use, more severe, perhaps esophageal or systemic fungal infection may be observed,” Dr. Feldman said in a recent editorial.

“Not knowing the future may make some physicians reticent about using the drug when other options are available, at least until data are available on much larger numbers of exposed patients treated for longer periods of time,” he and his colleague William Huang, MD, also a dermatologist at Wake Forest, said.

One of the limits of the trial was that the head-to-head portion was only 24 weeks, “which was too brief for a comparison of safety between bimekizumab and adalimumab in a lifelong disease,” the investigators noted.

The mean age of the patients was 44.9 years, and the mean baseline PASI score was 19.8.

Although the initial dose of adalimumab in the study was 40 mg, labeling recommends an initial dose of 80 mg for the TNF blocker.

Bimekizumab is also being evaluated in phase 3 trials for psoriatic arthritis, ankylosing spondylitis, nonradiographic axial spondyloarthritis, and hidradenitis suppurativa, according to UCB Pharma.

The study was funded by UCB Pharma. The investigators had numerous disclosures, including Dr. Warren who reported grants and personal fees from the company. Dr. Feldman reported receiving research, speaking, and/or consulting support from UCB Pharma and other companies.

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

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Quicker fertility rebound in young women with breast cancer

Article Type
Changed
Thu, 12/15/2022 - 17:29

Results from a phase 3 trial indicate that removing cyclophosphamide from standard chemotherapy can improve fertility without compromising survival in women with breast cancer.

Researchers found that omitting cyclophosphamide from a regimen of epirubicin and paclitaxel increased the likelihood of an early return of menses, and there was a trend toward improved disease-free survival.

The phase 3 SPECTRUM trial involved 521 women with estrogen receptor–positive, HER2-negative breast cancer who had undergone definitive surgery at one of eight institutions in China. The average age of the patients was 34 years.

Cyclophosphamide is a standard component of adjuvant chemotherapy, but it’s strongly associated with premature ovarian failure and infertility.

“For the first time, we demonstrate that a cyclophosphamide-free regimen [can] increase the rate of menses recovery without compromising survival,” said the researchers, led by Ke-Da Yu, MD, PhD, of the Fudan University Shanghai (China) Cancer Center.

They also reported that, among the women who tried to conceive at a later date, there was a higher pregnancy success rate among those who did not take cyclophosphamide.

“Our findings can be extrapolated to patients with other subtypes of breast cancer, such as triple-negative or HER2-enriched, because the effect of paclitaxel and cyclophosphamide on menstrual resumption is not subtype specific,” the investigators commented.

The results were published online in the Journal of the National Cancer Institute.

This is the first prospective trial specifically designed to find an adjuvant breast cancer regimen less toxic to the ovaries. The “investigators ... should be applauded,” wrote Matteo Lambertini, MD, PhD, of the University of Genova (Italy), and Ann Partridge, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

Although promising, there are a few caveats, the editorialists wrote. In a past trial of doxorubicin and docetaxel in lieu of a cyclophosphamide regimen, disease outcomes were inferior. There is also a question as to whether the SPECTRUM results apply to non-Asian women.

The editorialists also noted that enrollment in this trial ended in 2016, before it was recommended that ovarian suppression be used in conjunction with adjuvant chemotherapy to prevent premature menopause.

“[It’s] notable that the absolute benefit in reducing [premature ovarian insufficiency] rates with the use of a cyclophosphamide-free regimen is similar to the effect demonstrated with the administration of a gonadotropin-releasing hormone agonist during cyclophosphamide-based chemotherapy,” they commented. It’s possible that combining the two approaches might have an additive effect, but for now the possibility remains unknown.

In addition, the SPECTRUM trial predates the widespread use of genetic testing to guide treatment, the editorialists pointed out.

“Therefore, caution should be taken in adopting wholesale such regimens,” Dr. Lambertini and Dr. Partridge said.
 

Switch to paclitaxel

The research team was inspired by previous reports that swapping out cyclophosphamide for paclitaxel did not reduce adjuvant efficacy in the general breast cancer population.

The SPECTRUM trial randomly assigned 260 women to receive a cyclophosphamide-free regimen of epirubicin (75 mg/m2) and paclitaxel (175 mg/m2) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m2) for 12 weeks.

Another 261 women were randomly assigned to receive cyclophosphamide (600 mg/m2) and epirubicin (75 mg/m2) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m2) for 12 weeks. These patients constituted the control group.

A year after completing chemotherapy, 63.1% of the cyclophosphamide-free arm versus 48.3% of the control group, had resumed menses, defined as having two consecutive menstrual cycles or one cycle but with premenopausal levels of estradiol and follicle-stimulating hormone (P < .001).

Another caveat of the study is that assessments of women who resumed menses were conducted at the 1-year point; rates may have been higher in the cyclophosphamide arm had the investigators conducted the assessments at 2 years, the editorialists said.

The 5-year disease-free survival was 84.7% in the cyclophosphamide-free arm versus 78.3% in the control group, an absolute difference of 14.8% (P = .07).

Patients with node-positive disease appeared to benefit the most from cyclophosphamide sparing.

There were no statistically significant differences in overall or distant disease-free survival.
 

 

 

Higher pregnancy rates

Almost 18% of women in the experimental arm reported trying to conceive, and 9.6% of them did so. About 10% of women in the cyclophosphamide arm tried to conceive, and 2.7% did so (P = .03).

The median interval between randomization and pregnancy was 42 months.

For all of the women who became pregnant, endocrine therapy was interrupted. “Women who temporarily interrupt endocrine therapy due to pregnancy should be reminded to resume endocrine therapy following attempted or successful pregnancy,” the investigators wrote.

The patients were taking tamoxifen at least 5 years after receiving chemotherapy, most often as monotherapy. About 5% of the patients underwent up-front ovarian suppression with an aromatase inhibitor, which is a current standard option.

The study was supported by the National Natural Science Foundation of China and other organizations. The investigators and Dr. Partridge disclosed no relevant financial relationships. Dr. Lambertini has consulted for and/or has received speakers fees from Roche, AstraZeneca, Lilly, Novartis, and other companies.

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

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Results from a phase 3 trial indicate that removing cyclophosphamide from standard chemotherapy can improve fertility without compromising survival in women with breast cancer.

Researchers found that omitting cyclophosphamide from a regimen of epirubicin and paclitaxel increased the likelihood of an early return of menses, and there was a trend toward improved disease-free survival.

The phase 3 SPECTRUM trial involved 521 women with estrogen receptor–positive, HER2-negative breast cancer who had undergone definitive surgery at one of eight institutions in China. The average age of the patients was 34 years.

Cyclophosphamide is a standard component of adjuvant chemotherapy, but it’s strongly associated with premature ovarian failure and infertility.

“For the first time, we demonstrate that a cyclophosphamide-free regimen [can] increase the rate of menses recovery without compromising survival,” said the researchers, led by Ke-Da Yu, MD, PhD, of the Fudan University Shanghai (China) Cancer Center.

They also reported that, among the women who tried to conceive at a later date, there was a higher pregnancy success rate among those who did not take cyclophosphamide.

“Our findings can be extrapolated to patients with other subtypes of breast cancer, such as triple-negative or HER2-enriched, because the effect of paclitaxel and cyclophosphamide on menstrual resumption is not subtype specific,” the investigators commented.

The results were published online in the Journal of the National Cancer Institute.

This is the first prospective trial specifically designed to find an adjuvant breast cancer regimen less toxic to the ovaries. The “investigators ... should be applauded,” wrote Matteo Lambertini, MD, PhD, of the University of Genova (Italy), and Ann Partridge, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

Although promising, there are a few caveats, the editorialists wrote. In a past trial of doxorubicin and docetaxel in lieu of a cyclophosphamide regimen, disease outcomes were inferior. There is also a question as to whether the SPECTRUM results apply to non-Asian women.

The editorialists also noted that enrollment in this trial ended in 2016, before it was recommended that ovarian suppression be used in conjunction with adjuvant chemotherapy to prevent premature menopause.

“[It’s] notable that the absolute benefit in reducing [premature ovarian insufficiency] rates with the use of a cyclophosphamide-free regimen is similar to the effect demonstrated with the administration of a gonadotropin-releasing hormone agonist during cyclophosphamide-based chemotherapy,” they commented. It’s possible that combining the two approaches might have an additive effect, but for now the possibility remains unknown.

In addition, the SPECTRUM trial predates the widespread use of genetic testing to guide treatment, the editorialists pointed out.

“Therefore, caution should be taken in adopting wholesale such regimens,” Dr. Lambertini and Dr. Partridge said.
 

Switch to paclitaxel

The research team was inspired by previous reports that swapping out cyclophosphamide for paclitaxel did not reduce adjuvant efficacy in the general breast cancer population.

The SPECTRUM trial randomly assigned 260 women to receive a cyclophosphamide-free regimen of epirubicin (75 mg/m2) and paclitaxel (175 mg/m2) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m2) for 12 weeks.

Another 261 women were randomly assigned to receive cyclophosphamide (600 mg/m2) and epirubicin (75 mg/m2) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m2) for 12 weeks. These patients constituted the control group.

A year after completing chemotherapy, 63.1% of the cyclophosphamide-free arm versus 48.3% of the control group, had resumed menses, defined as having two consecutive menstrual cycles or one cycle but with premenopausal levels of estradiol and follicle-stimulating hormone (P < .001).

Another caveat of the study is that assessments of women who resumed menses were conducted at the 1-year point; rates may have been higher in the cyclophosphamide arm had the investigators conducted the assessments at 2 years, the editorialists said.

The 5-year disease-free survival was 84.7% in the cyclophosphamide-free arm versus 78.3% in the control group, an absolute difference of 14.8% (P = .07).

Patients with node-positive disease appeared to benefit the most from cyclophosphamide sparing.

There were no statistically significant differences in overall or distant disease-free survival.
 

 

 

Higher pregnancy rates

Almost 18% of women in the experimental arm reported trying to conceive, and 9.6% of them did so. About 10% of women in the cyclophosphamide arm tried to conceive, and 2.7% did so (P = .03).

The median interval between randomization and pregnancy was 42 months.

For all of the women who became pregnant, endocrine therapy was interrupted. “Women who temporarily interrupt endocrine therapy due to pregnancy should be reminded to resume endocrine therapy following attempted or successful pregnancy,” the investigators wrote.

The patients were taking tamoxifen at least 5 years after receiving chemotherapy, most often as monotherapy. About 5% of the patients underwent up-front ovarian suppression with an aromatase inhibitor, which is a current standard option.

The study was supported by the National Natural Science Foundation of China and other organizations. The investigators and Dr. Partridge disclosed no relevant financial relationships. Dr. Lambertini has consulted for and/or has received speakers fees from Roche, AstraZeneca, Lilly, Novartis, and other companies.

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

Results from a phase 3 trial indicate that removing cyclophosphamide from standard chemotherapy can improve fertility without compromising survival in women with breast cancer.

Researchers found that omitting cyclophosphamide from a regimen of epirubicin and paclitaxel increased the likelihood of an early return of menses, and there was a trend toward improved disease-free survival.

The phase 3 SPECTRUM trial involved 521 women with estrogen receptor–positive, HER2-negative breast cancer who had undergone definitive surgery at one of eight institutions in China. The average age of the patients was 34 years.

Cyclophosphamide is a standard component of adjuvant chemotherapy, but it’s strongly associated with premature ovarian failure and infertility.

“For the first time, we demonstrate that a cyclophosphamide-free regimen [can] increase the rate of menses recovery without compromising survival,” said the researchers, led by Ke-Da Yu, MD, PhD, of the Fudan University Shanghai (China) Cancer Center.

They also reported that, among the women who tried to conceive at a later date, there was a higher pregnancy success rate among those who did not take cyclophosphamide.

“Our findings can be extrapolated to patients with other subtypes of breast cancer, such as triple-negative or HER2-enriched, because the effect of paclitaxel and cyclophosphamide on menstrual resumption is not subtype specific,” the investigators commented.

The results were published online in the Journal of the National Cancer Institute.

This is the first prospective trial specifically designed to find an adjuvant breast cancer regimen less toxic to the ovaries. The “investigators ... should be applauded,” wrote Matteo Lambertini, MD, PhD, of the University of Genova (Italy), and Ann Partridge, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

Although promising, there are a few caveats, the editorialists wrote. In a past trial of doxorubicin and docetaxel in lieu of a cyclophosphamide regimen, disease outcomes were inferior. There is also a question as to whether the SPECTRUM results apply to non-Asian women.

The editorialists also noted that enrollment in this trial ended in 2016, before it was recommended that ovarian suppression be used in conjunction with adjuvant chemotherapy to prevent premature menopause.

“[It’s] notable that the absolute benefit in reducing [premature ovarian insufficiency] rates with the use of a cyclophosphamide-free regimen is similar to the effect demonstrated with the administration of a gonadotropin-releasing hormone agonist during cyclophosphamide-based chemotherapy,” they commented. It’s possible that combining the two approaches might have an additive effect, but for now the possibility remains unknown.

In addition, the SPECTRUM trial predates the widespread use of genetic testing to guide treatment, the editorialists pointed out.

“Therefore, caution should be taken in adopting wholesale such regimens,” Dr. Lambertini and Dr. Partridge said.
 

Switch to paclitaxel

The research team was inspired by previous reports that swapping out cyclophosphamide for paclitaxel did not reduce adjuvant efficacy in the general breast cancer population.

The SPECTRUM trial randomly assigned 260 women to receive a cyclophosphamide-free regimen of epirubicin (75 mg/m2) and paclitaxel (175 mg/m2) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m2) for 12 weeks.

Another 261 women were randomly assigned to receive cyclophosphamide (600 mg/m2) and epirubicin (75 mg/m2) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m2) for 12 weeks. These patients constituted the control group.

A year after completing chemotherapy, 63.1% of the cyclophosphamide-free arm versus 48.3% of the control group, had resumed menses, defined as having two consecutive menstrual cycles or one cycle but with premenopausal levels of estradiol and follicle-stimulating hormone (P < .001).

Another caveat of the study is that assessments of women who resumed menses were conducted at the 1-year point; rates may have been higher in the cyclophosphamide arm had the investigators conducted the assessments at 2 years, the editorialists said.

The 5-year disease-free survival was 84.7% in the cyclophosphamide-free arm versus 78.3% in the control group, an absolute difference of 14.8% (P = .07).

Patients with node-positive disease appeared to benefit the most from cyclophosphamide sparing.

There were no statistically significant differences in overall or distant disease-free survival.
 

 

 

Higher pregnancy rates

Almost 18% of women in the experimental arm reported trying to conceive, and 9.6% of them did so. About 10% of women in the cyclophosphamide arm tried to conceive, and 2.7% did so (P = .03).

The median interval between randomization and pregnancy was 42 months.

For all of the women who became pregnant, endocrine therapy was interrupted. “Women who temporarily interrupt endocrine therapy due to pregnancy should be reminded to resume endocrine therapy following attempted or successful pregnancy,” the investigators wrote.

The patients were taking tamoxifen at least 5 years after receiving chemotherapy, most often as monotherapy. About 5% of the patients underwent up-front ovarian suppression with an aromatase inhibitor, which is a current standard option.

The study was supported by the National Natural Science Foundation of China and other organizations. The investigators and Dr. Partridge disclosed no relevant financial relationships. Dr. Lambertini has consulted for and/or has received speakers fees from Roche, AstraZeneca, Lilly, Novartis, and other companies.

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

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