AVAHO

“Therapeutic innovations like elranatamab achieve a lasting response in 61% of patients with multiple myeloma and complete remission in 30%,” said María Victoria Mateos, MD, PhD, a consultant physician in the Hematology Service at the University Clinical Hospital of Salamanca, Spain, and president of the Spanish Society of Haematology and Haemotherapy.

“The introduction of treatments such as elranatamab (Elrexfio) is allowing patients with multiple myeloma, which is still incurable for now, to have different options and achieve long periods of remission, thus improving their survival,” she added. “This therapeutic innovation is highly effective and well tolerated in patients with relapse or refractory multiple myeloma.” The overall response rate is “up to 61%, early, deep, and long-lasting.”

In an interview with El Médico Interactivo, Dr. Mateos explained the new approaches to multiple myeloma. She highlighted the effectiveness of new treatments and reviewed the latest data on this disease, which were presented at the recent European Hematology Association Congress.
 

What is the incidence rate of multiple myeloma in the Spanish population?

Multiple myeloma has an incidence of approximately 4-5 new cases per 100,000 inhabitants per year. This means that around 3000 new cases are diagnosed each year in Spain. As with most tumors, multiple myeloma is generally slightly more common in males than females. It is the third most frequent hematologic cancer in men (1757 new cases) and women (1325 new cases), behind lymphoma and leukemias.

At what age is it most often diagnosed?

It affects older people, with recent reports indicating around 68-69 years as the median age. Although more young people are being diagnosed with multiple myeloma, analyses of how this hematologic cancer affects the general population show that it generally impacts patients over age 65 years.

What is the typical survival prognosis?

Thanks to research and therapeutic innovation, the prognosis has changed significantly over the past 20-25 years. Today, if a patient with multiple myeloma receives a diagnosis and does not exhibit poor prognostic characteristics (and this description fits approximately 70%-80% of patients with multiple myeloma), it is realistic to expect a survival exceeding 10 years. A few years ago, this outcome was unimaginable, but a significant amount of therapeutic innovation has made it possible. That’s why I emphasize that it is realistic to provide these data with such a positive outlook.

Is multiple myeloma a refractory type of cancer?

It was a refractory type of cancer. Twenty years ago, there were no treatment options, and therefore survival was around 2-3 years, because treatment mainly consisted of using alkylating agents and corticosteroids. This is what made it refractory.

With the emergence of new therapeutic innovations, patients have been responding better and their responses are lasting longer. Although there is still a group of patients, about 10%-15%, with a poor prognosis and refractory disease, those with standard risk are responding better to different therapies.

Although most patients will eventually exhaust the treatments, which until now were primarily triple-drug regimens (such as proteasome inhibitors, immunomodulators, and antiCD38 antibodies), the introduction of new therapies is extending the duration of responses.
 

Is the risk for relapse high?

It is very high, in the sense that almost all patients with multiple myeloma eventually relapse. However, we hope that there soon will be some patients who do not relapse.

What are the typical pathologic manifestations of this cancer? Does it affect everyone equally, or in specific ways in each person?

In multiple myeloma, we often say there are multiple myelomas. Clinically, the disease presents in most patients, around 80%, with two clinical manifestations: anemia and bone lesions. Less frequently, patients may also have kidney failure, hypercalcemia, and a higher tendency toward infection. Behind this rather common symptomatology, from a molecular and genetic perspective, each myeloma is practically unique, adding complexity to its treatment. Therefore, ultimately, myelomas end up being refractory.

Elranatamab is a new therapeutic tool. For which patients is it recommended?

It is a bispecific monoclonal antibody that corresponds to the new monotherapy strategies we have for treating patients with multiple myeloma. On the one hand, it targets damaged plasma cells, which are the patient’s tumor cells, and on the other, it binds the patient’s T cells and redirects them to the tumor niche. When this happens, the T cell activates and destroys the tumor cell.

This medication has been approved for patients with relapsed myeloma who have received traditional drugs for their treatment. We know well that patients who have already received proteasome inhibitors, immunomodulators, and anti-CD38 antibodies typically need something new after treatment. Before, there were no other options, and we would reuse what had been previously used. Now we have elranatamab, a bispecific monoclonal antibody targeting a new receptor that has shown significant responses as monotherapy.

More than 60% of patients respond, and more than 30% achieve complete remission. The key is the response duration and progression-free survival of almost a year and a half. This is the longest progression-free survival we have seen to date in previous lines. Therefore, it fills the needs we had for these relapsed or refractory myeloma patients.
 

What advantages does this new treatment offer?

It represents a therapeutic innovation because, as mentioned, it achieves a response in more than 60% of patients, and around 35% achieve complete remission. The median response duration has not been reached yet. Progression-free survival is 17.2 months, almost a year and a half, and overall survival is almost two years. 

Furthermore, it is administered as subcutaneous monotherapy weekly for the first six cycles and then every 15 days. It has a good safety profile, although some adverse events are known, so we have strategies to combat or mitigate them, making the treatment generally well tolerated.
 

What side effects are being observed?

They are manageable. When the drug is first administered, patients may experience what we call a cytokine release syndrome, which is a result of the treatment’s mechanism. However, we can predict very well when it occurs, usually 2 days after the first doses, and we have strategies to mitigate it.

The second most common adverse event we need to be cautious about is infection. Nowadays, before starting treatment, patients update their vaccination schedule, receive antiviral prophylaxis, and receive prophylaxis against certain germs, resulting in reduced infections. However, infections are probably the adverse events we need to be most careful about when treating the patient.

We must ensure that prophylaxis is performed, and if fever occurs and an infection is suspected, cultures and all kinds of studies must be done to identify and treat it properly.
 

How does elranatamab change the treatment of an incurable disease? Does it bring us closer to a cure or to making multiple myeloma a manageable chronic disease?

With the already approved elranatamab, the most important aspect is that it adds another treatment option for patients with myeloma. With the progression-free survival data I indicated, life expectancy is increased, with a good quality of life and acceptable safety.

Obviously, elranatamab is still under study and development, even in early lines, including in patients with newly diagnosed myeloma. When we are choosing first-line therapy, we select the best patients by combining traditional drugs with these new immunotherapies, such as elranatamab, it is likely that we are much closer to offering a cure to specific subgroups.

Although it won’t happen in all cases, I believe it will be applicable to a significant subgroup of patients, making chronicity of the disease a reality we are already approaching. Each day, we encounter more patients receiving different lines of treatment and ultimately meeting their life expectancy with myeloma. Even though some may die, it is often due to causes not related to myeloma. This is the most important contribution of these innovations, such as elranatamab.
 

Dr. Mateos reported receiving honoraria from Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Stemline, Oncopeptides, and Kite for delivering lectures and for participating in advisory boards. 

This story was translated from El Médico Interactivo, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

“Therapeutic innovations like elranatamab achieve a lasting response in 61% of patients with multiple myeloma and complete remission in 30%,” said María Victoria Mateos, MD, PhD, a consultant physician in the Hematology Service at the University Clinical Hospital of Salamanca, Spain, and president of the Spanish Society of Haematology and Haemotherapy.

“The introduction of treatments such as elranatamab (Elrexfio) is allowing patients with multiple myeloma, which is still incurable for now, to have different options and achieve long periods of remission, thus improving their survival,” she added. “This therapeutic innovation is highly effective and well tolerated in patients with relapse or refractory multiple myeloma.” The overall response rate is “up to 61%, early, deep, and long-lasting.”

In an interview with El Médico Interactivo, Dr. Mateos explained the new approaches to multiple myeloma. She highlighted the effectiveness of new treatments and reviewed the latest data on this disease, which were presented at the recent European Hematology Association Congress.
 

What is the incidence rate of multiple myeloma in the Spanish population?

Multiple myeloma has an incidence of approximately 4-5 new cases per 100,000 inhabitants per year. This means that around 3000 new cases are diagnosed each year in Spain. As with most tumors, multiple myeloma is generally slightly more common in males than females. It is the third most frequent hematologic cancer in men (1757 new cases) and women (1325 new cases), behind lymphoma and leukemias.

At what age is it most often diagnosed?

It affects older people, with recent reports indicating around 68-69 years as the median age. Although more young people are being diagnosed with multiple myeloma, analyses of how this hematologic cancer affects the general population show that it generally impacts patients over age 65 years.

What is the typical survival prognosis?

Thanks to research and therapeutic innovation, the prognosis has changed significantly over the past 20-25 years. Today, if a patient with multiple myeloma receives a diagnosis and does not exhibit poor prognostic characteristics (and this description fits approximately 70%-80% of patients with multiple myeloma), it is realistic to expect a survival exceeding 10 years. A few years ago, this outcome was unimaginable, but a significant amount of therapeutic innovation has made it possible. That’s why I emphasize that it is realistic to provide these data with such a positive outlook.

Is multiple myeloma a refractory type of cancer?

It was a refractory type of cancer. Twenty years ago, there were no treatment options, and therefore survival was around 2-3 years, because treatment mainly consisted of using alkylating agents and corticosteroids. This is what made it refractory.

With the emergence of new therapeutic innovations, patients have been responding better and their responses are lasting longer. Although there is still a group of patients, about 10%-15%, with a poor prognosis and refractory disease, those with standard risk are responding better to different therapies.

Although most patients will eventually exhaust the treatments, which until now were primarily triple-drug regimens (such as proteasome inhibitors, immunomodulators, and antiCD38 antibodies), the introduction of new therapies is extending the duration of responses.
 

Is the risk for relapse high?

It is very high, in the sense that almost all patients with multiple myeloma eventually relapse. However, we hope that there soon will be some patients who do not relapse.

What are the typical pathologic manifestations of this cancer? Does it affect everyone equally, or in specific ways in each person?

In multiple myeloma, we often say there are multiple myelomas. Clinically, the disease presents in most patients, around 80%, with two clinical manifestations: anemia and bone lesions. Less frequently, patients may also have kidney failure, hypercalcemia, and a higher tendency toward infection. Behind this rather common symptomatology, from a molecular and genetic perspective, each myeloma is practically unique, adding complexity to its treatment. Therefore, ultimately, myelomas end up being refractory.

Elranatamab is a new therapeutic tool. For which patients is it recommended?

It is a bispecific monoclonal antibody that corresponds to the new monotherapy strategies we have for treating patients with multiple myeloma. On the one hand, it targets damaged plasma cells, which are the patient’s tumor cells, and on the other, it binds the patient’s T cells and redirects them to the tumor niche. When this happens, the T cell activates and destroys the tumor cell.

This medication has been approved for patients with relapsed myeloma who have received traditional drugs for their treatment. We know well that patients who have already received proteasome inhibitors, immunomodulators, and anti-CD38 antibodies typically need something new after treatment. Before, there were no other options, and we would reuse what had been previously used. Now we have elranatamab, a bispecific monoclonal antibody targeting a new receptor that has shown significant responses as monotherapy.

More than 60% of patients respond, and more than 30% achieve complete remission. The key is the response duration and progression-free survival of almost a year and a half. This is the longest progression-free survival we have seen to date in previous lines. Therefore, it fills the needs we had for these relapsed or refractory myeloma patients.
 

What advantages does this new treatment offer?

It represents a therapeutic innovation because, as mentioned, it achieves a response in more than 60% of patients, and around 35% achieve complete remission. The median response duration has not been reached yet. Progression-free survival is 17.2 months, almost a year and a half, and overall survival is almost two years. 

Furthermore, it is administered as subcutaneous monotherapy weekly for the first six cycles and then every 15 days. It has a good safety profile, although some adverse events are known, so we have strategies to combat or mitigate them, making the treatment generally well tolerated.
 

What side effects are being observed?

They are manageable. When the drug is first administered, patients may experience what we call a cytokine release syndrome, which is a result of the treatment’s mechanism. However, we can predict very well when it occurs, usually 2 days after the first doses, and we have strategies to mitigate it.

The second most common adverse event we need to be cautious about is infection. Nowadays, before starting treatment, patients update their vaccination schedule, receive antiviral prophylaxis, and receive prophylaxis against certain germs, resulting in reduced infections. However, infections are probably the adverse events we need to be most careful about when treating the patient.

We must ensure that prophylaxis is performed, and if fever occurs and an infection is suspected, cultures and all kinds of studies must be done to identify and treat it properly.
 

How does elranatamab change the treatment of an incurable disease? Does it bring us closer to a cure or to making multiple myeloma a manageable chronic disease?

With the already approved elranatamab, the most important aspect is that it adds another treatment option for patients with myeloma. With the progression-free survival data I indicated, life expectancy is increased, with a good quality of life and acceptable safety.

Obviously, elranatamab is still under study and development, even in early lines, including in patients with newly diagnosed myeloma. When we are choosing first-line therapy, we select the best patients by combining traditional drugs with these new immunotherapies, such as elranatamab, it is likely that we are much closer to offering a cure to specific subgroups.

Although it won’t happen in all cases, I believe it will be applicable to a significant subgroup of patients, making chronicity of the disease a reality we are already approaching. Each day, we encounter more patients receiving different lines of treatment and ultimately meeting their life expectancy with myeloma. Even though some may die, it is often due to causes not related to myeloma. This is the most important contribution of these innovations, such as elranatamab.
 

Dr. Mateos reported receiving honoraria from Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Stemline, Oncopeptides, and Kite for delivering lectures and for participating in advisory boards. 

This story was translated from El Médico Interactivo, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

“Therapeutic innovations like elranatamab achieve a lasting response in 61% of patients with multiple myeloma and complete remission in 30%,” said María Victoria Mateos, MD, PhD, a consultant physician in the Hematology Service at the University Clinical Hospital of Salamanca, Spain, and president of the Spanish Society of Haematology and Haemotherapy.

“The introduction of treatments such as elranatamab (Elrexfio) is allowing patients with multiple myeloma, which is still incurable for now, to have different options and achieve long periods of remission, thus improving their survival,” she added. “This therapeutic innovation is highly effective and well tolerated in patients with relapse or refractory multiple myeloma.” The overall response rate is “up to 61%, early, deep, and long-lasting.”

In an interview with El Médico Interactivo, Dr. Mateos explained the new approaches to multiple myeloma. She highlighted the effectiveness of new treatments and reviewed the latest data on this disease, which were presented at the recent European Hematology Association Congress.
 

What is the incidence rate of multiple myeloma in the Spanish population?

Multiple myeloma has an incidence of approximately 4-5 new cases per 100,000 inhabitants per year. This means that around 3000 new cases are diagnosed each year in Spain. As with most tumors, multiple myeloma is generally slightly more common in males than females. It is the third most frequent hematologic cancer in men (1757 new cases) and women (1325 new cases), behind lymphoma and leukemias.

At what age is it most often diagnosed?

It affects older people, with recent reports indicating around 68-69 years as the median age. Although more young people are being diagnosed with multiple myeloma, analyses of how this hematologic cancer affects the general population show that it generally impacts patients over age 65 years.

What is the typical survival prognosis?

Thanks to research and therapeutic innovation, the prognosis has changed significantly over the past 20-25 years. Today, if a patient with multiple myeloma receives a diagnosis and does not exhibit poor prognostic characteristics (and this description fits approximately 70%-80% of patients with multiple myeloma), it is realistic to expect a survival exceeding 10 years. A few years ago, this outcome was unimaginable, but a significant amount of therapeutic innovation has made it possible. That’s why I emphasize that it is realistic to provide these data with such a positive outlook.

Is multiple myeloma a refractory type of cancer?

It was a refractory type of cancer. Twenty years ago, there were no treatment options, and therefore survival was around 2-3 years, because treatment mainly consisted of using alkylating agents and corticosteroids. This is what made it refractory.

With the emergence of new therapeutic innovations, patients have been responding better and their responses are lasting longer. Although there is still a group of patients, about 10%-15%, with a poor prognosis and refractory disease, those with standard risk are responding better to different therapies.

Although most patients will eventually exhaust the treatments, which until now were primarily triple-drug regimens (such as proteasome inhibitors, immunomodulators, and antiCD38 antibodies), the introduction of new therapies is extending the duration of responses.
 

Is the risk for relapse high?

It is very high, in the sense that almost all patients with multiple myeloma eventually relapse. However, we hope that there soon will be some patients who do not relapse.

What are the typical pathologic manifestations of this cancer? Does it affect everyone equally, or in specific ways in each person?

In multiple myeloma, we often say there are multiple myelomas. Clinically, the disease presents in most patients, around 80%, with two clinical manifestations: anemia and bone lesions. Less frequently, patients may also have kidney failure, hypercalcemia, and a higher tendency toward infection. Behind this rather common symptomatology, from a molecular and genetic perspective, each myeloma is practically unique, adding complexity to its treatment. Therefore, ultimately, myelomas end up being refractory.

Elranatamab is a new therapeutic tool. For which patients is it recommended?

It is a bispecific monoclonal antibody that corresponds to the new monotherapy strategies we have for treating patients with multiple myeloma. On the one hand, it targets damaged plasma cells, which are the patient’s tumor cells, and on the other, it binds the patient’s T cells and redirects them to the tumor niche. When this happens, the T cell activates and destroys the tumor cell.

This medication has been approved for patients with relapsed myeloma who have received traditional drugs for their treatment. We know well that patients who have already received proteasome inhibitors, immunomodulators, and anti-CD38 antibodies typically need something new after treatment. Before, there were no other options, and we would reuse what had been previously used. Now we have elranatamab, a bispecific monoclonal antibody targeting a new receptor that has shown significant responses as monotherapy.

More than 60% of patients respond, and more than 30% achieve complete remission. The key is the response duration and progression-free survival of almost a year and a half. This is the longest progression-free survival we have seen to date in previous lines. Therefore, it fills the needs we had for these relapsed or refractory myeloma patients.
 

What advantages does this new treatment offer?

It represents a therapeutic innovation because, as mentioned, it achieves a response in more than 60% of patients, and around 35% achieve complete remission. The median response duration has not been reached yet. Progression-free survival is 17.2 months, almost a year and a half, and overall survival is almost two years. 

Furthermore, it is administered as subcutaneous monotherapy weekly for the first six cycles and then every 15 days. It has a good safety profile, although some adverse events are known, so we have strategies to combat or mitigate them, making the treatment generally well tolerated.
 

What side effects are being observed?

They are manageable. When the drug is first administered, patients may experience what we call a cytokine release syndrome, which is a result of the treatment’s mechanism. However, we can predict very well when it occurs, usually 2 days after the first doses, and we have strategies to mitigate it.

The second most common adverse event we need to be cautious about is infection. Nowadays, before starting treatment, patients update their vaccination schedule, receive antiviral prophylaxis, and receive prophylaxis against certain germs, resulting in reduced infections. However, infections are probably the adverse events we need to be most careful about when treating the patient.

We must ensure that prophylaxis is performed, and if fever occurs and an infection is suspected, cultures and all kinds of studies must be done to identify and treat it properly.
 

How does elranatamab change the treatment of an incurable disease? Does it bring us closer to a cure or to making multiple myeloma a manageable chronic disease?

With the already approved elranatamab, the most important aspect is that it adds another treatment option for patients with myeloma. With the progression-free survival data I indicated, life expectancy is increased, with a good quality of life and acceptable safety.

Obviously, elranatamab is still under study and development, even in early lines, including in patients with newly diagnosed myeloma. When we are choosing first-line therapy, we select the best patients by combining traditional drugs with these new immunotherapies, such as elranatamab, it is likely that we are much closer to offering a cure to specific subgroups.

Although it won’t happen in all cases, I believe it will be applicable to a significant subgroup of patients, making chronicity of the disease a reality we are already approaching. Each day, we encounter more patients receiving different lines of treatment and ultimately meeting their life expectancy with myeloma. Even though some may die, it is often due to causes not related to myeloma. This is the most important contribution of these innovations, such as elranatamab.
 

Dr. Mateos reported receiving honoraria from Janssen, Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, Stemline, Oncopeptides, and Kite for delivering lectures and for participating in advisory boards. 

This story was translated from El Médico Interactivo, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lazertinib (Lazcluze) in combination with amivantamab-vmjw (Rybrevant) for upfront treatment of adults with locally advanced or metastatic non–small-cell lung cancer (NSCLC) who have EGFR exon 19 deletions or exon 21 L858R substitution mutations as detected by an FDA-approved test. 

This marks the first approval for lazertinib. Amivantamab was initially approved by the FDA in 2021 and carries a few indications for locally advanced or metastatic NSCLC. Both drugs are manufactured by Janssen Biotech Inc.

“Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” study investigator Alexander Spira, MD, PhD, director, Virginia Cancer Specialists Research Institute, said in a news release from Johnson & Johnson . 

Lazertinib is an oral, highly selective, third-generation EGFR tyrosine kinase inhibitor that can penetrate the brain and amivantamab is a bispecific antibody targeting EGFR and MET.

The approval was based on results from the phase 3 MARIPOSA trial, which showed that the combination reduced the risk of disease progression or death by 30% compared with osimertinib.

The MARIPOSA trial randomly allocated 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease to amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.

Lazertinib plus amivantamab demonstrated a statistically significant improvement in progression-free survival compared with osimertinib (hazard ratio, 0.70; P < .001). Median progression-free survival was 23.7 months with the combination vs 16.6 months osimertinib alone and 18.5 months with lazertinib alone.

The median duration of response was 9 months longer with the combination compared with osimertinib (25.8 months vs 16.7 months).

The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. 

“A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy,” the FDA noted in a statement announcing the approval.

Results from MARIPOSA were first presented at the European Society for Medical Oncology 2023 Congress and published in The New England Journal of Medicine in June. Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer in September.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lazertinib (Lazcluze) in combination with amivantamab-vmjw (Rybrevant) for upfront treatment of adults with locally advanced or metastatic non–small-cell lung cancer (NSCLC) who have EGFR exon 19 deletions or exon 21 L858R substitution mutations as detected by an FDA-approved test. 

This marks the first approval for lazertinib. Amivantamab was initially approved by the FDA in 2021 and carries a few indications for locally advanced or metastatic NSCLC. Both drugs are manufactured by Janssen Biotech Inc.

“Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” study investigator Alexander Spira, MD, PhD, director, Virginia Cancer Specialists Research Institute, said in a news release from Johnson & Johnson . 

Lazertinib is an oral, highly selective, third-generation EGFR tyrosine kinase inhibitor that can penetrate the brain and amivantamab is a bispecific antibody targeting EGFR and MET.

The approval was based on results from the phase 3 MARIPOSA trial, which showed that the combination reduced the risk of disease progression or death by 30% compared with osimertinib.

The MARIPOSA trial randomly allocated 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease to amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.

Lazertinib plus amivantamab demonstrated a statistically significant improvement in progression-free survival compared with osimertinib (hazard ratio, 0.70; P < .001). Median progression-free survival was 23.7 months with the combination vs 16.6 months osimertinib alone and 18.5 months with lazertinib alone.

The median duration of response was 9 months longer with the combination compared with osimertinib (25.8 months vs 16.7 months).

The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. 

“A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy,” the FDA noted in a statement announcing the approval.

Results from MARIPOSA were first presented at the European Society for Medical Oncology 2023 Congress and published in The New England Journal of Medicine in June. Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer in September.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved lazertinib (Lazcluze) in combination with amivantamab-vmjw (Rybrevant) for upfront treatment of adults with locally advanced or metastatic non–small-cell lung cancer (NSCLC) who have EGFR exon 19 deletions or exon 21 L858R substitution mutations as detected by an FDA-approved test. 

This marks the first approval for lazertinib. Amivantamab was initially approved by the FDA in 2021 and carries a few indications for locally advanced or metastatic NSCLC. Both drugs are manufactured by Janssen Biotech Inc.

“Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib,” study investigator Alexander Spira, MD, PhD, director, Virginia Cancer Specialists Research Institute, said in a news release from Johnson & Johnson . 

Lazertinib is an oral, highly selective, third-generation EGFR tyrosine kinase inhibitor that can penetrate the brain and amivantamab is a bispecific antibody targeting EGFR and MET.

The approval was based on results from the phase 3 MARIPOSA trial, which showed that the combination reduced the risk of disease progression or death by 30% compared with osimertinib.

The MARIPOSA trial randomly allocated 1074 patients with exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC and no prior systemic therapy for advanced disease to amivantamab plus lazertinib, osimertinib alone, or lazertinib alone.

Lazertinib plus amivantamab demonstrated a statistically significant improvement in progression-free survival compared with osimertinib (hazard ratio, 0.70; P < .001). Median progression-free survival was 23.7 months with the combination vs 16.6 months osimertinib alone and 18.5 months with lazertinib alone.

The median duration of response was 9 months longer with the combination compared with osimertinib (25.8 months vs 16.7 months).

The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reactions (amivantamab), musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity. 

“A serious safety signal of venous thromboembolic events was observed with lazertinib in combination with amivantamab and prophylactic anticoagulation should be administered for the first four months of therapy,” the FDA noted in a statement announcing the approval.

Results from MARIPOSA were first presented at the European Society for Medical Oncology 2023 Congress and published in The New England Journal of Medicine in June. Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer 2024 World Congress on Lung Cancer in September.
 

A version of this article appeared on Medscape.com.

Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office. 

The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.

In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
 

Meeting the Criteria

The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:

• The disease that the test screens for must have a presymptomatic form.
• The screening test must be able to identify this presymptomatic disease.
• Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
• The screening test is feasible, and the benefits outweigh potential risks.

“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.

The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
 

Inappropriate Endpoints?

Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.

Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.

“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”

Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.
 

An NHS Study

Arguments for different endpoints apparently resonated with the United Kingdom’s National Health Service (NHS). Three years ago, they initiated the Galleri study, a large randomized controlled trial to assess the effectiveness of Grail’s cancer test. The primary endpoint was not cancer-specific mortality, but the incidence of stage III or IV cancer.

The results are expected in 2026. But recruitment was stopped after 140,000 participants were enrolled. The NHS reported that the initial results were not convincing enough to continue the trial. Exact numbers were not disclosed.

The Galleri study deviates from the standard randomized controlled trial design for cancer screening procedures not only in terms of the primary endpoint, but also in blinding. The only participants who were unblinded and informed of their test results are those in the intervention group with a positive cancer test.
 

False Security

This trial design encourages participants to undergo blood tests once per year. But according to Dr. Robbins, it prevents the exploration of the phenomenon of “false security,” which is a potential drawback of the new cancer tests.

“Women with a negative mammogram can reasonably assume that they probably do not have breast cancer. But individuals with a negative cancer blood test could mistakenly believe they cannot have any cancer at all. As a result, they may not undergo standard early detection screenings or seek medical help early enough for potential cancer symptoms,” said Dr. Robbins.

To assess the actual risk-benefit ratio of the Galleri test, participants must receive their test results, she said. “Under real-world conditions, benefits and risks can come from positive and negative results.” 
 

Upcoming Trial

More illuminating results may come from a large trial planned by the National Cancer Institute in the United States. Several new cancer tests will be evaluated for their ability to reduce cancer-specific mortality. A pilot phase will start later in 2024. “This study may be the only one with sufficient statistical power to determine whether an approach based on these cancer tests can reduce cancer-specific mortality,” said Dr. Robbins.

For the new blood tests for multiple cancers, it is crucial that health authorities “set a high bar for a benefit,” she said. This, according to her, also means that they must show an effect on cancer-specific mortality before being introduced. “This evidence must come from studies in which commercial interests do not influence the design, execution, data management, or data analysis.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version appeared on Medscape.com.

Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office. 

The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.

In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
 

Meeting the Criteria

The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:

• The disease that the test screens for must have a presymptomatic form.
• The screening test must be able to identify this presymptomatic disease.
• Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
• The screening test is feasible, and the benefits outweigh potential risks.

“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.

The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
 

Inappropriate Endpoints?

Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.

Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.

“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”

Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.
 

An NHS Study

Arguments for different endpoints apparently resonated with the United Kingdom’s National Health Service (NHS). Three years ago, they initiated the Galleri study, a large randomized controlled trial to assess the effectiveness of Grail’s cancer test. The primary endpoint was not cancer-specific mortality, but the incidence of stage III or IV cancer.

The results are expected in 2026. But recruitment was stopped after 140,000 participants were enrolled. The NHS reported that the initial results were not convincing enough to continue the trial. Exact numbers were not disclosed.

The Galleri study deviates from the standard randomized controlled trial design for cancer screening procedures not only in terms of the primary endpoint, but also in blinding. The only participants who were unblinded and informed of their test results are those in the intervention group with a positive cancer test.
 

False Security

This trial design encourages participants to undergo blood tests once per year. But according to Dr. Robbins, it prevents the exploration of the phenomenon of “false security,” which is a potential drawback of the new cancer tests.

“Women with a negative mammogram can reasonably assume that they probably do not have breast cancer. But individuals with a negative cancer blood test could mistakenly believe they cannot have any cancer at all. As a result, they may not undergo standard early detection screenings or seek medical help early enough for potential cancer symptoms,” said Dr. Robbins.

To assess the actual risk-benefit ratio of the Galleri test, participants must receive their test results, she said. “Under real-world conditions, benefits and risks can come from positive and negative results.” 
 

Upcoming Trial

More illuminating results may come from a large trial planned by the National Cancer Institute in the United States. Several new cancer tests will be evaluated for their ability to reduce cancer-specific mortality. A pilot phase will start later in 2024. “This study may be the only one with sufficient statistical power to determine whether an approach based on these cancer tests can reduce cancer-specific mortality,” said Dr. Robbins.

For the new blood tests for multiple cancers, it is crucial that health authorities “set a high bar for a benefit,” she said. This, according to her, also means that they must show an effect on cancer-specific mortality before being introduced. “This evidence must come from studies in which commercial interests do not influence the design, execution, data management, or data analysis.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version appeared on Medscape.com.

Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office. 

The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.

In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
 

Meeting the Criteria

The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:

• The disease that the test screens for must have a presymptomatic form.
• The screening test must be able to identify this presymptomatic disease.
• Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
• The screening test is feasible, and the benefits outweigh potential risks.

“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.

The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
 

Inappropriate Endpoints?

Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.

Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.

“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”

Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.
 

An NHS Study

Arguments for different endpoints apparently resonated with the United Kingdom’s National Health Service (NHS). Three years ago, they initiated the Galleri study, a large randomized controlled trial to assess the effectiveness of Grail’s cancer test. The primary endpoint was not cancer-specific mortality, but the incidence of stage III or IV cancer.

The results are expected in 2026. But recruitment was stopped after 140,000 participants were enrolled. The NHS reported that the initial results were not convincing enough to continue the trial. Exact numbers were not disclosed.

The Galleri study deviates from the standard randomized controlled trial design for cancer screening procedures not only in terms of the primary endpoint, but also in blinding. The only participants who were unblinded and informed of their test results are those in the intervention group with a positive cancer test.
 

False Security

This trial design encourages participants to undergo blood tests once per year. But according to Dr. Robbins, it prevents the exploration of the phenomenon of “false security,” which is a potential drawback of the new cancer tests.

“Women with a negative mammogram can reasonably assume that they probably do not have breast cancer. But individuals with a negative cancer blood test could mistakenly believe they cannot have any cancer at all. As a result, they may not undergo standard early detection screenings or seek medical help early enough for potential cancer symptoms,” said Dr. Robbins.

To assess the actual risk-benefit ratio of the Galleri test, participants must receive their test results, she said. “Under real-world conditions, benefits and risks can come from positive and negative results.” 
 

Upcoming Trial

More illuminating results may come from a large trial planned by the National Cancer Institute in the United States. Several new cancer tests will be evaluated for their ability to reduce cancer-specific mortality. A pilot phase will start later in 2024. “This study may be the only one with sufficient statistical power to determine whether an approach based on these cancer tests can reduce cancer-specific mortality,” said Dr. Robbins.

For the new blood tests for multiple cancers, it is crucial that health authorities “set a high bar for a benefit,” she said. This, according to her, also means that they must show an effect on cancer-specific mortality before being introduced. “This evidence must come from studies in which commercial interests do not influence the design, execution, data management, or data analysis.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version appeared on Medscape.com.

Having an ostomy is a dreaded prospect for many patients with rectal cancer.

To defer, and potentially avoid, this life-altering surgery, the watch-and-wait approach has become increasingly common among patients with locally advanced disease who have a complete response to neoadjuvant chemoradiation.

About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.

The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.

But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.

“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.

A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.

The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.

But there’s no clear way to predict which tumors will evolve into a clinical complete response.

Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.

Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.

A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.

But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.

And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
 

Selecting Patients for Watch-and-Wait

The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.

OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.

The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.

UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.

Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.

For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.

For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.

Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.

Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.

If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.

As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”

Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.

The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.

However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.

Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
 

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

Having an ostomy is a dreaded prospect for many patients with rectal cancer.

To defer, and potentially avoid, this life-altering surgery, the watch-and-wait approach has become increasingly common among patients with locally advanced disease who have a complete response to neoadjuvant chemoradiation.

About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.

The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.

But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.

“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.

A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.

The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.

But there’s no clear way to predict which tumors will evolve into a clinical complete response.

Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.

Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.

A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.

But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.

And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
 

Selecting Patients for Watch-and-Wait

The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.

OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.

The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.

UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.

Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.

For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.

For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.

Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.

Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.

If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.

As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”

Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.

The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.

However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.

Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
 

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

Having an ostomy is a dreaded prospect for many patients with rectal cancer.

To defer, and potentially avoid, this life-altering surgery, the watch-and-wait approach has become increasingly common among patients with locally advanced disease who have a complete response to neoadjuvant chemoradiation.

About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.

The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.

But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.

“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.

A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.

The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.

But there’s no clear way to predict which tumors will evolve into a clinical complete response.

Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.

Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.

A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.

But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.

And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
 

Selecting Patients for Watch-and-Wait

The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.

OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.

The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.

UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.

Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.

For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.

For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.

Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.

Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.

If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.

As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”

Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.

The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.

However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.

Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
 

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

The Food and Drug Administration (FDA) has approved durvalumab (Imfinzi; AstraZeneca) both before and after surgery in patients with resectable non–small cell lung cancer (NSCLC) without EGFR mutations or ALK rearrangements. The agency approved durvalumab alongside platinum-containing chemotherapy in the neoadjuvant setting and as monotherapy in the adjuvant setting.

The approval comes shortly after a meeting of FDA’s Oncology Drug Advisory Committee, where agency personnel took AstraZeneca to task for not following its request to include an arm in the approval study, AEGEAN, to clarify whether or not treatment after surgery was necessary. 

Even so, advisers at the July 25 meeting voted “yes” to approving the neoadjuvant/adjuvant indication to give patients another immunotherapy option in NSCLC. However, the committee voted unanimously that, going forward, the agency should require — instead of simply request — that companies seeking combined neoadjuvant/adjuvant NSCLC indications show that patients actually need treatment after surgery. 

The new approval is durvalumab’s first indication for resectable NSCLC. The agent has been previously approved for unresectable or metastatic disease as well as extensive-stage small cell lung cancer, locally advanced or metastatic biliary tract cancer, unresectable hepatocellular carcinoma, and advanced or recurrent endometrial cancer. 

AEGEAN included 802 patients with previously untreated and resectable stage IIA-IIIB squamous or nonsquamous NSCLC. Patients were randomly assigned to receive either durvalumab (400 patients) or placebo (402 patients) on a background of platinum-based chemotherapy every 3 weeks for four cycles then, following surgery, durvalumab or placebo once a month for a year. 

The pathologic complete response rate was 17% in the durvalumab arm vs 4.3% in the placebo arm. At 12 months, event-free survival was 73.4% with durvalumab vs 64.5% with placebo. Overall survival differences have not been tested for statistical significance, but there was “no clear detriment” with durvalumab, FDA said in a press release. 

Adverse reactions in 20% or more of durvalumab recipients included anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash; 1.7% of durvalumab recipients and 1% of placebo recipients could not have surgery because of side effects during neoadjuvant treatment. 

The dosage for patients weighing > 30 kg is 1500 mg every 3 weeks before surgery and every 4 weeks afterward. For patients who weigh less than that, the recommended dosage is 20 mg/kg. 

Durvalumab costs around $1,053 for 120 mg, according to drugs.com.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved durvalumab (Imfinzi; AstraZeneca) both before and after surgery in patients with resectable non–small cell lung cancer (NSCLC) without EGFR mutations or ALK rearrangements. The agency approved durvalumab alongside platinum-containing chemotherapy in the neoadjuvant setting and as monotherapy in the adjuvant setting.

The approval comes shortly after a meeting of FDA’s Oncology Drug Advisory Committee, where agency personnel took AstraZeneca to task for not following its request to include an arm in the approval study, AEGEAN, to clarify whether or not treatment after surgery was necessary. 

Even so, advisers at the July 25 meeting voted “yes” to approving the neoadjuvant/adjuvant indication to give patients another immunotherapy option in NSCLC. However, the committee voted unanimously that, going forward, the agency should require — instead of simply request — that companies seeking combined neoadjuvant/adjuvant NSCLC indications show that patients actually need treatment after surgery. 

The new approval is durvalumab’s first indication for resectable NSCLC. The agent has been previously approved for unresectable or metastatic disease as well as extensive-stage small cell lung cancer, locally advanced or metastatic biliary tract cancer, unresectable hepatocellular carcinoma, and advanced or recurrent endometrial cancer. 

AEGEAN included 802 patients with previously untreated and resectable stage IIA-IIIB squamous or nonsquamous NSCLC. Patients were randomly assigned to receive either durvalumab (400 patients) or placebo (402 patients) on a background of platinum-based chemotherapy every 3 weeks for four cycles then, following surgery, durvalumab or placebo once a month for a year. 

The pathologic complete response rate was 17% in the durvalumab arm vs 4.3% in the placebo arm. At 12 months, event-free survival was 73.4% with durvalumab vs 64.5% with placebo. Overall survival differences have not been tested for statistical significance, but there was “no clear detriment” with durvalumab, FDA said in a press release. 

Adverse reactions in 20% or more of durvalumab recipients included anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash; 1.7% of durvalumab recipients and 1% of placebo recipients could not have surgery because of side effects during neoadjuvant treatment. 

The dosage for patients weighing > 30 kg is 1500 mg every 3 weeks before surgery and every 4 weeks afterward. For patients who weigh less than that, the recommended dosage is 20 mg/kg. 

Durvalumab costs around $1,053 for 120 mg, according to drugs.com.

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved durvalumab (Imfinzi; AstraZeneca) both before and after surgery in patients with resectable non–small cell lung cancer (NSCLC) without EGFR mutations or ALK rearrangements. The agency approved durvalumab alongside platinum-containing chemotherapy in the neoadjuvant setting and as monotherapy in the adjuvant setting.

The approval comes shortly after a meeting of FDA’s Oncology Drug Advisory Committee, where agency personnel took AstraZeneca to task for not following its request to include an arm in the approval study, AEGEAN, to clarify whether or not treatment after surgery was necessary. 

Even so, advisers at the July 25 meeting voted “yes” to approving the neoadjuvant/adjuvant indication to give patients another immunotherapy option in NSCLC. However, the committee voted unanimously that, going forward, the agency should require — instead of simply request — that companies seeking combined neoadjuvant/adjuvant NSCLC indications show that patients actually need treatment after surgery. 

The new approval is durvalumab’s first indication for resectable NSCLC. The agent has been previously approved for unresectable or metastatic disease as well as extensive-stage small cell lung cancer, locally advanced or metastatic biliary tract cancer, unresectable hepatocellular carcinoma, and advanced or recurrent endometrial cancer. 

AEGEAN included 802 patients with previously untreated and resectable stage IIA-IIIB squamous or nonsquamous NSCLC. Patients were randomly assigned to receive either durvalumab (400 patients) or placebo (402 patients) on a background of platinum-based chemotherapy every 3 weeks for four cycles then, following surgery, durvalumab or placebo once a month for a year. 

The pathologic complete response rate was 17% in the durvalumab arm vs 4.3% in the placebo arm. At 12 months, event-free survival was 73.4% with durvalumab vs 64.5% with placebo. Overall survival differences have not been tested for statistical significance, but there was “no clear detriment” with durvalumab, FDA said in a press release. 

Adverse reactions in 20% or more of durvalumab recipients included anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash; 1.7% of durvalumab recipients and 1% of placebo recipients could not have surgery because of side effects during neoadjuvant treatment. 

The dosage for patients weighing > 30 kg is 1500 mg every 3 weeks before surgery and every 4 weeks afterward. For patients who weigh less than that, the recommended dosage is 20 mg/kg. 

Durvalumab costs around $1,053 for 120 mg, according to drugs.com.

A version of this article appeared on Medscape.com.

BRCA1 and BRCA2 pathogenic variants carry well-known associations with breast and ovarian cancers in women, which has led to robust clinical guidelines for early genetic testing and risk-reduction strategies. 

Male carriers of BRCA1/2 pathogenic variants also face an increased risk for cancer, particularly of the prostate, pancreas, and breast. 

However, men often fly under the radar. 

Although males represent half of BRCA1/2 pathogenic variant carriers, men are much less likely to receive genetic testing for BRCA mutations. “Most people (including their clinicians) are unaware of their carrier status,” Heather Cheng, MD, PhD, with University of Washington, Seattle, and colleagues explained in a comprehensive review on the subject, published in JAMA Oncology. Most are also unaware of “the associated cancer risks, and management recommendations” for BRCA carriers. 

The testing gap in males may exist, in part, because of a “general lack of awareness” that BRCA gene mutations can be passed down to children from both the mother and father, Elisa Port, MD, chief of breast surgery for the Mount Sinai Health System in New York City, told this news organization.

A daughter can inherit a mutated BRCA gene that puts her at risk for breast or ovarian cancer from her mother’s or father’s family and, similarly, a son can inherit a mutated BRCA gene from either side of the family that puts him at an increased risk for developing prostate and other cancers, explained Dr. Port, director of the Center of Excellence for Breast Cancer at The Tisch Cancer Institute at Mount Sinai. 

Considering family history and genetics on both sides of the family is important when assessing cancer risk in men and women, Dr. Port said. 
 

BRCA Mutations in Men: What’s the Risk? 

Although fewer than 1% of all breast cancers occur in men, when men do carry a BRCA mutation, their risk for breast cancer can increase considerably. The lifetime risk for breast cancer can be as high as 9% in male BRCA2 carriers and up to 1.2% in BRCA1 carriers. 

BRCA1/2 mutations also put men at increased risk for pancreatic and prostate cancers.

For pancreatic cancer, male BRCA1 carriers have a nearly twofold increased risk compared with the general population, with a lifetime risk of 3%. BRCA2 carriers have a three- to nearly eightfold increased risk, with a lifetime risk up to 7%.

Male BRCA1 carriers face a nearly fourfold increased risk of developing prostate cancer and an absolute lifetime risk of 15%-45%. Male BRCA2 carriers have a five- to ninefold increased risk for prostate cancer, with an absolute lifetime risk between 27% and 60%. 
 

When to Test, When to Screen?

Despite the increased risk for several cancers associated with BRCA mutations, many men are not offered genetic testing.

BRCA1/2 genetic testing in men is “ultra-important but underutilized and is an evolving unmet need that the field needs to address,” Kai Tsao, MD MS, medical director of the Medical Oncology Prostate Cancer Program at Mount Sinai in New York City, told this news organization. 

For men considering genetic testing, in Dr. Tsao’s experience, barriers may include fear that insurance may not cover the test and that a positive test may increase insurance premiums, as well as concerns about what the test result may mean for them and their family.

Even for confirmed BRCA carriers, cancer screening guidelines for men vary.

For breast screening in men, there’s limited data to inform guidelines. The National Cancer Center Network currently recommends breast awareness and teaching self-examination starting at age 35 and recommends men with BRCA variants consider yearly mammograms starting at age 50, or 10 years before the earliest male breast cancer diagnosis in the family. 

Data show that screening mammography in men at high-risk for breast cancer yields similar cancer detection rates in men and women, “suggesting mammography screening may be valuable in male BRCA carriers,” the review authors noted. And, in a recent study of men with BRCA1/2 pathogenic variants, most (71%) recommended for screening mammography completed their screening. 

The European Society for Medical Oncology (ESMO) has similar screening recommendations but focuses only on men with BRCA2 mutations and suggests breast ultrasonography as well as mammography as a screening option.

The larger “issue is the general population doesn’t think of breast cancer when they think of men, which may delay seeking medical attention,” said Melissa Fana, MD, of NYU Grossman Long Island School of Medicine and NYU Langone Health, who wasn’t involved in the review. 

For pancreatic cancer, guidelines suggest BRCA1/2 carriers be screened for pancreatic cancer starting at age 50, or 10 years before the earliest known pancreatic cancer in the family, although the guidelines vary on the role family history should play.

And for prostate cancer, current guidelines recommend male BRCA carriers begin prostate-specific antigen screening between age 40 and 45 years, although recommendations on screening intervals and start age vary. ESMO recommendations are similar but only apply to BRCA2 carriers.

A male patient with a BRCA1/2 variant is typically referred for genetic counseling as well, Dr. Tsao explained. But “the challenge is that we don’t have a very good healthcare infrastructure right now” to follow through with that, he added. “Oftentimes a patient will wait many months or even more than a year for a genetic counseling appointment.”

To help improve these issues, Mount Sinai recently launched a comprehensive BRCA program for men and women that offers genetic testing and counseling for patients and family members.

Overall, identifying more male BRCA1/2 carriers will “maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer,” Dr. Cheng and colleagues concluded.

Support for the review was provided in part by BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA. Cheng reported grants from Promontory Pharmaceutics, Medivation, Sanofi, Janssen, royalties from UpToDate, nonfinancial support from Color Health, personal fees from AstraZeneca, BRCA Research and Cure Alliance (CureBRCA) outside the submitted work. Dr. Port, Dr. Tsao, and Dr. Fana had no conflicts of interest.
 

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

BRCA1 and BRCA2 pathogenic variants carry well-known associations with breast and ovarian cancers in women, which has led to robust clinical guidelines for early genetic testing and risk-reduction strategies. 

Male carriers of BRCA1/2 pathogenic variants also face an increased risk for cancer, particularly of the prostate, pancreas, and breast. 

However, men often fly under the radar. 

Although males represent half of BRCA1/2 pathogenic variant carriers, men are much less likely to receive genetic testing for BRCA mutations. “Most people (including their clinicians) are unaware of their carrier status,” Heather Cheng, MD, PhD, with University of Washington, Seattle, and colleagues explained in a comprehensive review on the subject, published in JAMA Oncology. Most are also unaware of “the associated cancer risks, and management recommendations” for BRCA carriers. 

The testing gap in males may exist, in part, because of a “general lack of awareness” that BRCA gene mutations can be passed down to children from both the mother and father, Elisa Port, MD, chief of breast surgery for the Mount Sinai Health System in New York City, told this news organization.

A daughter can inherit a mutated BRCA gene that puts her at risk for breast or ovarian cancer from her mother’s or father’s family and, similarly, a son can inherit a mutated BRCA gene from either side of the family that puts him at an increased risk for developing prostate and other cancers, explained Dr. Port, director of the Center of Excellence for Breast Cancer at The Tisch Cancer Institute at Mount Sinai. 

Considering family history and genetics on both sides of the family is important when assessing cancer risk in men and women, Dr. Port said. 
 

BRCA Mutations in Men: What’s the Risk? 

Although fewer than 1% of all breast cancers occur in men, when men do carry a BRCA mutation, their risk for breast cancer can increase considerably. The lifetime risk for breast cancer can be as high as 9% in male BRCA2 carriers and up to 1.2% in BRCA1 carriers. 

BRCA1/2 mutations also put men at increased risk for pancreatic and prostate cancers.

For pancreatic cancer, male BRCA1 carriers have a nearly twofold increased risk compared with the general population, with a lifetime risk of 3%. BRCA2 carriers have a three- to nearly eightfold increased risk, with a lifetime risk up to 7%.

Male BRCA1 carriers face a nearly fourfold increased risk of developing prostate cancer and an absolute lifetime risk of 15%-45%. Male BRCA2 carriers have a five- to ninefold increased risk for prostate cancer, with an absolute lifetime risk between 27% and 60%. 
 

When to Test, When to Screen?

Despite the increased risk for several cancers associated with BRCA mutations, many men are not offered genetic testing.

BRCA1/2 genetic testing in men is “ultra-important but underutilized and is an evolving unmet need that the field needs to address,” Kai Tsao, MD MS, medical director of the Medical Oncology Prostate Cancer Program at Mount Sinai in New York City, told this news organization. 

For men considering genetic testing, in Dr. Tsao’s experience, barriers may include fear that insurance may not cover the test and that a positive test may increase insurance premiums, as well as concerns about what the test result may mean for them and their family.

Even for confirmed BRCA carriers, cancer screening guidelines for men vary.

For breast screening in men, there’s limited data to inform guidelines. The National Cancer Center Network currently recommends breast awareness and teaching self-examination starting at age 35 and recommends men with BRCA variants consider yearly mammograms starting at age 50, or 10 years before the earliest male breast cancer diagnosis in the family. 

Data show that screening mammography in men at high-risk for breast cancer yields similar cancer detection rates in men and women, “suggesting mammography screening may be valuable in male BRCA carriers,” the review authors noted. And, in a recent study of men with BRCA1/2 pathogenic variants, most (71%) recommended for screening mammography completed their screening. 

The European Society for Medical Oncology (ESMO) has similar screening recommendations but focuses only on men with BRCA2 mutations and suggests breast ultrasonography as well as mammography as a screening option.

The larger “issue is the general population doesn’t think of breast cancer when they think of men, which may delay seeking medical attention,” said Melissa Fana, MD, of NYU Grossman Long Island School of Medicine and NYU Langone Health, who wasn’t involved in the review. 

For pancreatic cancer, guidelines suggest BRCA1/2 carriers be screened for pancreatic cancer starting at age 50, or 10 years before the earliest known pancreatic cancer in the family, although the guidelines vary on the role family history should play.

And for prostate cancer, current guidelines recommend male BRCA carriers begin prostate-specific antigen screening between age 40 and 45 years, although recommendations on screening intervals and start age vary. ESMO recommendations are similar but only apply to BRCA2 carriers.

A male patient with a BRCA1/2 variant is typically referred for genetic counseling as well, Dr. Tsao explained. But “the challenge is that we don’t have a very good healthcare infrastructure right now” to follow through with that, he added. “Oftentimes a patient will wait many months or even more than a year for a genetic counseling appointment.”

To help improve these issues, Mount Sinai recently launched a comprehensive BRCA program for men and women that offers genetic testing and counseling for patients and family members.

Overall, identifying more male BRCA1/2 carriers will “maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer,” Dr. Cheng and colleagues concluded.

Support for the review was provided in part by BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA. Cheng reported grants from Promontory Pharmaceutics, Medivation, Sanofi, Janssen, royalties from UpToDate, nonfinancial support from Color Health, personal fees from AstraZeneca, BRCA Research and Cure Alliance (CureBRCA) outside the submitted work. Dr. Port, Dr. Tsao, and Dr. Fana had no conflicts of interest.
 

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

BRCA1 and BRCA2 pathogenic variants carry well-known associations with breast and ovarian cancers in women, which has led to robust clinical guidelines for early genetic testing and risk-reduction strategies. 

Male carriers of BRCA1/2 pathogenic variants also face an increased risk for cancer, particularly of the prostate, pancreas, and breast. 

However, men often fly under the radar. 

Although males represent half of BRCA1/2 pathogenic variant carriers, men are much less likely to receive genetic testing for BRCA mutations. “Most people (including their clinicians) are unaware of their carrier status,” Heather Cheng, MD, PhD, with University of Washington, Seattle, and colleagues explained in a comprehensive review on the subject, published in JAMA Oncology. Most are also unaware of “the associated cancer risks, and management recommendations” for BRCA carriers. 

The testing gap in males may exist, in part, because of a “general lack of awareness” that BRCA gene mutations can be passed down to children from both the mother and father, Elisa Port, MD, chief of breast surgery for the Mount Sinai Health System in New York City, told this news organization.

A daughter can inherit a mutated BRCA gene that puts her at risk for breast or ovarian cancer from her mother’s or father’s family and, similarly, a son can inherit a mutated BRCA gene from either side of the family that puts him at an increased risk for developing prostate and other cancers, explained Dr. Port, director of the Center of Excellence for Breast Cancer at The Tisch Cancer Institute at Mount Sinai. 

Considering family history and genetics on both sides of the family is important when assessing cancer risk in men and women, Dr. Port said. 
 

BRCA Mutations in Men: What’s the Risk? 

Although fewer than 1% of all breast cancers occur in men, when men do carry a BRCA mutation, their risk for breast cancer can increase considerably. The lifetime risk for breast cancer can be as high as 9% in male BRCA2 carriers and up to 1.2% in BRCA1 carriers. 

BRCA1/2 mutations also put men at increased risk for pancreatic and prostate cancers.

For pancreatic cancer, male BRCA1 carriers have a nearly twofold increased risk compared with the general population, with a lifetime risk of 3%. BRCA2 carriers have a three- to nearly eightfold increased risk, with a lifetime risk up to 7%.

Male BRCA1 carriers face a nearly fourfold increased risk of developing prostate cancer and an absolute lifetime risk of 15%-45%. Male BRCA2 carriers have a five- to ninefold increased risk for prostate cancer, with an absolute lifetime risk between 27% and 60%. 
 

When to Test, When to Screen?

Despite the increased risk for several cancers associated with BRCA mutations, many men are not offered genetic testing.

BRCA1/2 genetic testing in men is “ultra-important but underutilized and is an evolving unmet need that the field needs to address,” Kai Tsao, MD MS, medical director of the Medical Oncology Prostate Cancer Program at Mount Sinai in New York City, told this news organization. 

For men considering genetic testing, in Dr. Tsao’s experience, barriers may include fear that insurance may not cover the test and that a positive test may increase insurance premiums, as well as concerns about what the test result may mean for them and their family.

Even for confirmed BRCA carriers, cancer screening guidelines for men vary.

For breast screening in men, there’s limited data to inform guidelines. The National Cancer Center Network currently recommends breast awareness and teaching self-examination starting at age 35 and recommends men with BRCA variants consider yearly mammograms starting at age 50, or 10 years before the earliest male breast cancer diagnosis in the family. 

Data show that screening mammography in men at high-risk for breast cancer yields similar cancer detection rates in men and women, “suggesting mammography screening may be valuable in male BRCA carriers,” the review authors noted. And, in a recent study of men with BRCA1/2 pathogenic variants, most (71%) recommended for screening mammography completed their screening. 

The European Society for Medical Oncology (ESMO) has similar screening recommendations but focuses only on men with BRCA2 mutations and suggests breast ultrasonography as well as mammography as a screening option.

The larger “issue is the general population doesn’t think of breast cancer when they think of men, which may delay seeking medical attention,” said Melissa Fana, MD, of NYU Grossman Long Island School of Medicine and NYU Langone Health, who wasn’t involved in the review. 

For pancreatic cancer, guidelines suggest BRCA1/2 carriers be screened for pancreatic cancer starting at age 50, or 10 years before the earliest known pancreatic cancer in the family, although the guidelines vary on the role family history should play.

And for prostate cancer, current guidelines recommend male BRCA carriers begin prostate-specific antigen screening between age 40 and 45 years, although recommendations on screening intervals and start age vary. ESMO recommendations are similar but only apply to BRCA2 carriers.

A male patient with a BRCA1/2 variant is typically referred for genetic counseling as well, Dr. Tsao explained. But “the challenge is that we don’t have a very good healthcare infrastructure right now” to follow through with that, he added. “Oftentimes a patient will wait many months or even more than a year for a genetic counseling appointment.”

To help improve these issues, Mount Sinai recently launched a comprehensive BRCA program for men and women that offers genetic testing and counseling for patients and family members.

Overall, identifying more male BRCA1/2 carriers will “maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer,” Dr. Cheng and colleagues concluded.

Support for the review was provided in part by BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA. Cheng reported grants from Promontory Pharmaceutics, Medivation, Sanofi, Janssen, royalties from UpToDate, nonfinancial support from Color Health, personal fees from AstraZeneca, BRCA Research and Cure Alliance (CureBRCA) outside the submitted work. Dr. Port, Dr. Tsao, and Dr. Fana had no conflicts of interest.
 

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Artera, the Los Altos, California–based developer of tools to diagnose cancer, has launched the first artificial intelligence (AI) test to guide patients in making informed decisions between active surveillance and active treatment based on an analysis of digital pathology images.

Trevor Royce, MD, MPH, senior medical director of Artera, said the new version of the ArteraAI Prostate Test helps patients with low-risk (Grade Group 1/Gleason 6) to favorable intermediate-risk (Grade Group 2/Gleason 3+4) prostate cancer choose between treatment or active surveillance.

The test estimates how a patient’s cancer may progress and predicts the benefit of treatment for localized prostate cancer. 

“The prognostic performance of the test has now been validated in a diverse cohort of patients, including those who have undergone active surveillance, radiation therapy, or had a radical prostatectomy,” said Dr. Royce, a faculty member in radiation oncology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. “The prognostic risk result reflects the patient’s prognosis regardless of the treatment path chosen.”

Dr. Royce said the new test predicts the risk for developing distant metastasis in 10 years. For the population considering active surveillance, it also can predict the likelihood their cancer will show more aggressive features. The test does not make a clinical recommendation, he added.

“Ultimately, that’s a very personal decision between the patient and their physician, and we view it as supporting that decision-making process,” he said.

The test is available in all states but New York and California, where the company is now, in discussions with regulators for approval, according to Dr. Royce. He said the company is in discussion with private insurers to set reimbursement and payment rates. In January 2024, Medicare set a payment rate of $700 for the AI test, which carries no out-of-pocket costs for patients. 

The first indication for the test was for localized prostate cancer, prognosticating the risk for distant metastases and death from prostate cancer. It can also predict if an individual will benefit from androgen deprivation therapy (ADT). Dr. Royce said up to 60% of patients with intermediate risk prostate cancer now can avoid ADT and its serious side effects, such as brain fog, weight gain, and reduction in muscle mass.

In March, the National Comprehensive Cancer Network, an alliance of 33 cancer centers included Artera as the first AI test in its Clinical Practice Guidelines in Oncology.

Dr. Royce said active surveillance is a new application of the test. The test was initially developed on a foundational study of almost 22,000 pathology slides from nearly 7000 patients published in npj Digital Medicine in 2022.

Todd Morgan, MD, chief of the Division of Urologic Oncology at the University of Michigan in Ann Arbor, and coauthor of the foundational study, said the AI test adds another layer of data to making clinical decisions for lower-risk patients.

“The technology is a big deal. The ability to use digital images to make accurate prognostic estimates is pretty remarkable, and this is the first test in any disease site to do this,” Dr. Morgan said. “Ultimately, this means tests may someday be performed by just sending images rather than sending actual tissue to an outside laboratory. Is the AI test dramatically more accurate than the genomic platforms? That’s TBD [to be determined].”

Dr. Royce said Artera is now working on a version of its test to inform men with higher-risk prostate cancer how long ADT should last and what the prognosis is for patients who have undergone prostatectomy based on their surgical specimen. The current test uses samples from the prostate biopsy, which are processed in a central lab. 

Dr. Royce said the company would like to eventually perform the test using digital images of pathology slides only.

Dr. Morgan reported no conflicts of interest.
 

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

Artera, the Los Altos, California–based developer of tools to diagnose cancer, has launched the first artificial intelligence (AI) test to guide patients in making informed decisions between active surveillance and active treatment based on an analysis of digital pathology images.

Trevor Royce, MD, MPH, senior medical director of Artera, said the new version of the ArteraAI Prostate Test helps patients with low-risk (Grade Group 1/Gleason 6) to favorable intermediate-risk (Grade Group 2/Gleason 3+4) prostate cancer choose between treatment or active surveillance.

The test estimates how a patient’s cancer may progress and predicts the benefit of treatment for localized prostate cancer. 

“The prognostic performance of the test has now been validated in a diverse cohort of patients, including those who have undergone active surveillance, radiation therapy, or had a radical prostatectomy,” said Dr. Royce, a faculty member in radiation oncology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. “The prognostic risk result reflects the patient’s prognosis regardless of the treatment path chosen.”

Dr. Royce said the new test predicts the risk for developing distant metastasis in 10 years. For the population considering active surveillance, it also can predict the likelihood their cancer will show more aggressive features. The test does not make a clinical recommendation, he added.

“Ultimately, that’s a very personal decision between the patient and their physician, and we view it as supporting that decision-making process,” he said.

The test is available in all states but New York and California, where the company is now, in discussions with regulators for approval, according to Dr. Royce. He said the company is in discussion with private insurers to set reimbursement and payment rates. In January 2024, Medicare set a payment rate of $700 for the AI test, which carries no out-of-pocket costs for patients. 

The first indication for the test was for localized prostate cancer, prognosticating the risk for distant metastases and death from prostate cancer. It can also predict if an individual will benefit from androgen deprivation therapy (ADT). Dr. Royce said up to 60% of patients with intermediate risk prostate cancer now can avoid ADT and its serious side effects, such as brain fog, weight gain, and reduction in muscle mass.

In March, the National Comprehensive Cancer Network, an alliance of 33 cancer centers included Artera as the first AI test in its Clinical Practice Guidelines in Oncology.

Dr. Royce said active surveillance is a new application of the test. The test was initially developed on a foundational study of almost 22,000 pathology slides from nearly 7000 patients published in npj Digital Medicine in 2022.

Todd Morgan, MD, chief of the Division of Urologic Oncology at the University of Michigan in Ann Arbor, and coauthor of the foundational study, said the AI test adds another layer of data to making clinical decisions for lower-risk patients.

“The technology is a big deal. The ability to use digital images to make accurate prognostic estimates is pretty remarkable, and this is the first test in any disease site to do this,” Dr. Morgan said. “Ultimately, this means tests may someday be performed by just sending images rather than sending actual tissue to an outside laboratory. Is the AI test dramatically more accurate than the genomic platforms? That’s TBD [to be determined].”

Dr. Royce said Artera is now working on a version of its test to inform men with higher-risk prostate cancer how long ADT should last and what the prognosis is for patients who have undergone prostatectomy based on their surgical specimen. The current test uses samples from the prostate biopsy, which are processed in a central lab. 

Dr. Royce said the company would like to eventually perform the test using digital images of pathology slides only.

Dr. Morgan reported no conflicts of interest.
 

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

Artera, the Los Altos, California–based developer of tools to diagnose cancer, has launched the first artificial intelligence (AI) test to guide patients in making informed decisions between active surveillance and active treatment based on an analysis of digital pathology images.

Trevor Royce, MD, MPH, senior medical director of Artera, said the new version of the ArteraAI Prostate Test helps patients with low-risk (Grade Group 1/Gleason 6) to favorable intermediate-risk (Grade Group 2/Gleason 3+4) prostate cancer choose between treatment or active surveillance.

The test estimates how a patient’s cancer may progress and predicts the benefit of treatment for localized prostate cancer. 

“The prognostic performance of the test has now been validated in a diverse cohort of patients, including those who have undergone active surveillance, radiation therapy, or had a radical prostatectomy,” said Dr. Royce, a faculty member in radiation oncology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. “The prognostic risk result reflects the patient’s prognosis regardless of the treatment path chosen.”

Dr. Royce said the new test predicts the risk for developing distant metastasis in 10 years. For the population considering active surveillance, it also can predict the likelihood their cancer will show more aggressive features. The test does not make a clinical recommendation, he added.

“Ultimately, that’s a very personal decision between the patient and their physician, and we view it as supporting that decision-making process,” he said.

The test is available in all states but New York and California, where the company is now, in discussions with regulators for approval, according to Dr. Royce. He said the company is in discussion with private insurers to set reimbursement and payment rates. In January 2024, Medicare set a payment rate of $700 for the AI test, which carries no out-of-pocket costs for patients. 

The first indication for the test was for localized prostate cancer, prognosticating the risk for distant metastases and death from prostate cancer. It can also predict if an individual will benefit from androgen deprivation therapy (ADT). Dr. Royce said up to 60% of patients with intermediate risk prostate cancer now can avoid ADT and its serious side effects, such as brain fog, weight gain, and reduction in muscle mass.

In March, the National Comprehensive Cancer Network, an alliance of 33 cancer centers included Artera as the first AI test in its Clinical Practice Guidelines in Oncology.

Dr. Royce said active surveillance is a new application of the test. The test was initially developed on a foundational study of almost 22,000 pathology slides from nearly 7000 patients published in npj Digital Medicine in 2022.

Todd Morgan, MD, chief of the Division of Urologic Oncology at the University of Michigan in Ann Arbor, and coauthor of the foundational study, said the AI test adds another layer of data to making clinical decisions for lower-risk patients.

“The technology is a big deal. The ability to use digital images to make accurate prognostic estimates is pretty remarkable, and this is the first test in any disease site to do this,” Dr. Morgan said. “Ultimately, this means tests may someday be performed by just sending images rather than sending actual tissue to an outside laboratory. Is the AI test dramatically more accurate than the genomic platforms? That’s TBD [to be determined].”

Dr. Royce said Artera is now working on a version of its test to inform men with higher-risk prostate cancer how long ADT should last and what the prognosis is for patients who have undergone prostatectomy based on their surgical specimen. The current test uses samples from the prostate biopsy, which are processed in a central lab. 

Dr. Royce said the company would like to eventually perform the test using digital images of pathology slides only.

Dr. Morgan reported no conflicts of interest.
 

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

TOPLINE:

An easy-to-use web-based prognostic tool, MetroPancreas, may help predict the likelihood of futile pancreatectomy in patients with resectable pancreatic ductal adenocarcinoma and improve patient selection for upfront surgery.

METHODOLOGY:

• Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
• To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
• The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
• The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
• The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.

TAKEAWAY:

• The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
• Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
• The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
• Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).

IN PRACTICE:

“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.

SOURCE:

This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.

LIMITATIONS:

In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.

DISCLOSURES:

The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.

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

TOPLINE:

An easy-to-use web-based prognostic tool, MetroPancreas, may help predict the likelihood of futile pancreatectomy in patients with resectable pancreatic ductal adenocarcinoma and improve patient selection for upfront surgery.

METHODOLOGY:

• Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
• To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
• The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
• The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
• The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.

TAKEAWAY:

• The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
• Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
• The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
• Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).

IN PRACTICE:

“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.

SOURCE:

This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.

LIMITATIONS:

In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.

DISCLOSURES:

The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.

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

TOPLINE:

An easy-to-use web-based prognostic tool, MetroPancreas, may help predict the likelihood of futile pancreatectomy in patients with resectable pancreatic ductal adenocarcinoma and improve patient selection for upfront surgery.

METHODOLOGY:

• Immediate resection is associated with a high incidence of postoperative complications and disease recurrence within a year of surgery in patients with pancreatic ductal adenocarcinoma. Predicting which patients likely won’t benefit from upfront pancreatectomy is important.
• To identify preoperative risk factors for futile pancreatectomy, researchers evaluated 1426 patients (median age, 69 years; 53.2% men) with anatomically resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection between January 2010 and December 2021.
• The patients were divided into derivation (n = 885) and validation (n = 541) cohorts.
• The primary outcome was the rate of futile upfront pancreatectomy, defined as death or disease recurrence within 6 months of surgery. Patients were divided into three risk categories — low, intermediate, and high risk — each with escalating likelihoods of futile resection, worse pathological features, and worse outcomes.
• The secondary endpoint was to develop criteria for surgical candidacy, setting a futility likelihood threshold of < 20%. This threshold corresponds to the lower bound of the 95% confidence interval (CI) for postneoadjuvant resection rates (resection rate, 0.90; 95% CI, 0.80-1.01) from recent meta-analyses.

TAKEAWAY:

• The futility rate for pancreatectomy was 18.9% — 19.2% in the development cohort and 18.6% in the validation cohort. Three independent risk factors for futile resection included American Society of Anesthesiologists (ASA) class (95% CI for coefficients, 0.68-0.87), preoperative cancer antigen 19.9 serum levels (95% CI for coefficients, 0.05-0.75), and radiologic tumor size (95% CI for coefficients, 0.28-0.46).
• Using these independent risk factors, the predictive model demonstrated adequate calibration and discrimination in both the derivation and validation cohorts.
• The researchers then identified three risk groups. In the derivation cohort, the rate of futile pancreatectomy was 9.2% in the low-risk group, 18.0% in the intermediate-risk group, and 28.7% in the high-risk group (P < .001 for trend). In the validation cohort, the futility rate was 10.9% in the low-risk group, 20.2% in the intermediate-risk group, and 29.2% in the high-risk group (P < .001 for trend).
• Researchers identified four conditions associated with a futility likelihood below 20%, where larger tumor size is paired with lower cancer antigen 19.9 levels (defined as cancer antigen 19.9–adjusted-to-size). Patients who met these criteria experienced significantly longer disease-free survival (median 18.4 months vs 11.2 months) and overall survival (38.5 months vs 22.1 months).

IN PRACTICE:

“Although the study provides an easy-to-use calculator for clinical decision-making, there are some methodological limitations,” according to the authors of accompanying commentary. These limitations include failing to accurately describe how ASA class, cancer antigen 19.9 level, and tumor size were chosen for the model. “While we do not think the model is yet ready for standard clinical use, it may prove to be a viable tool if tested in future randomized trials comparing the neoadjuvant approach to upfront surgery in resectable pancreatic cancer,” the editorialists added.

SOURCE:

This study, led by Stefano Crippa, MD, PhD, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and the accompanying commentary were published online in JAMA Surgery.

LIMITATIONS:

In addition to the limitations noted by the editorialists, others include the study’s retrospective design, which could introduce bias. Because preoperative imaging was not revised, the assigned resectability classes could show variability. Institutional differences existed in the selection process for upfront pancreatectomy. The model cannot be applied to cancer antigen 19.9 nonsecretors and was not externally validated.

DISCLOSURES:

The Italian Association for Cancer Research Special Program in Metastatic Disease and Italian Ministry of Health/Italian Foundation for the Research of Pancreatic Diseases supported the study in the form of a grant. Two authors reported receiving personal fees outside the submitted work. No other disclosures were reported.

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