Lung Cancer

Each year in the United States, approximately 1.7 million Americans are diagnosed with a potentially lethal malignancy. Typical therapies of choice include surgery, radiation, and occasionally, toxic chemotherapy (chemo) — approaches that eliminate the cancer in about 1,000,000 of these cases. The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.

I’m speaking in generalities, understanding that each cancer and each patient is unique.
 

Chemotherapy

Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.

• Lack of response (the tumor failed to shrink).
• Progression (the cancer may have grown or spread further).
• Adverse side effects were too severe to continue.

The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.

Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:

• New or different chemotherapy drugs compared with prior lines.
• Surgery to debulk the tumor.
• Radiation for symptom control.
• Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
• Immunotherapy: agents that help the body’s immune system fight cancer cells.
• Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.

The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.

It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.

Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
 

Interventions to Consider Earlier

In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:

• Molecular testing.
• Palliation.
• Clinical trials.
• Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.

I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.

Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:

• Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
• Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
• Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.

Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.

Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.

Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.

Specific situations where discussing palliative care might be appropriate are:

• Soon after a cancer diagnosis.
• If the patient experiences significant side effects from cancer treatment.
• When considering different treatment options, palliative care can complement those treatments.
• In advanced stages of cancer, to focus on comfort and quality of life.

Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.

In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.

Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.

These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.

Read more about these leading innovations:

SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment

Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Using Live Cells from Patients to Find the Right Cancer Drug

Other innovative therapies under investigation could even be agnostic to cancer type:

Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?

High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.

Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Each year in the United States, approximately 1.7 million Americans are diagnosed with a potentially lethal malignancy. Typical therapies of choice include surgery, radiation, and occasionally, toxic chemotherapy (chemo) — approaches that eliminate the cancer in about 1,000,000 of these cases. The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.

I’m speaking in generalities, understanding that each cancer and each patient is unique.
 

Chemotherapy

Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.

• Lack of response (the tumor failed to shrink).
• Progression (the cancer may have grown or spread further).
• Adverse side effects were too severe to continue.

The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.

Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:

• New or different chemotherapy drugs compared with prior lines.
• Surgery to debulk the tumor.
• Radiation for symptom control.
• Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
• Immunotherapy: agents that help the body’s immune system fight cancer cells.
• Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.

The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.

It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.

Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
 

Interventions to Consider Earlier

In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:

• Molecular testing.
• Palliation.
• Clinical trials.
• Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.

I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.

Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:

• Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
• Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
• Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.

Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.

Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.

Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.

Specific situations where discussing palliative care might be appropriate are:

• Soon after a cancer diagnosis.
• If the patient experiences significant side effects from cancer treatment.
• When considering different treatment options, palliative care can complement those treatments.
• In advanced stages of cancer, to focus on comfort and quality of life.

Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.

In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.

Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.

These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.

Read more about these leading innovations:

SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment

Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Using Live Cells from Patients to Find the Right Cancer Drug

Other innovative therapies under investigation could even be agnostic to cancer type:

Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?

High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.

Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Each year in the United States, approximately 1.7 million Americans are diagnosed with a potentially lethal malignancy. Typical therapies of choice include surgery, radiation, and occasionally, toxic chemotherapy (chemo) — approaches that eliminate the cancer in about 1,000,000 of these cases. The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.

I’m speaking in generalities, understanding that each cancer and each patient is unique.
 

Chemotherapy

Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.

• Lack of response (the tumor failed to shrink).
• Progression (the cancer may have grown or spread further).
• Adverse side effects were too severe to continue.

The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.

Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:

• New or different chemotherapy drugs compared with prior lines.
• Surgery to debulk the tumor.
• Radiation for symptom control.
• Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
• Immunotherapy: agents that help the body’s immune system fight cancer cells.
• Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.

The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.

It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.

Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
 

Interventions to Consider Earlier

In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:

• Molecular testing.
• Palliation.
• Clinical trials.
• Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.

I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.

Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:

• Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
• Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
• Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.

Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.

Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.

Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.

Specific situations where discussing palliative care might be appropriate are:

• Soon after a cancer diagnosis.
• If the patient experiences significant side effects from cancer treatment.
• When considering different treatment options, palliative care can complement those treatments.
• In advanced stages of cancer, to focus on comfort and quality of life.

Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.

In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.

Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.

These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.

Read more about these leading innovations:

SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment

Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Using Live Cells from Patients to Find the Right Cancer Drug

Other innovative therapies under investigation could even be agnostic to cancer type:

Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?

High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.

Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.

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.

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

This story was translated from Univadis Italy 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.

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

This story was translated from Univadis Italy 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.

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

This story was translated from Univadis Italy 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.

TOPLINE:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various sources.

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:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various sources.

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:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various sources.

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.

An estimated 450,000 US deaths are expected this year from conditions attributed to cigarette smoking. Although the percentage of adults who smoke declined from 21% in 2005 to 11% in 2022, the annual death toll has been stable since 2005 and isn’t expected to decline until 2030, owing to an aging population of current and former smokers.

In 2022, based on a national survey, two thirds of the 28.8 million US adult smokers wanted to quit, and more than half tried quitting on their own or with the help of clinicians, but less than 9% succeeded in kicking the habit. The health benefits of quitting, summarized in a patient education handout from the American Cancer Society, include a lower risk for cancer, diabetes, and cardiovascular disease. Furthermore, the handout states, “quitting smoking can add as much as 10 years to your life, compared to if you continued to smoke.”

For my patients older than age 50 who are lifelong smokers, the qualifier “as much as” can be a sticking point. Although most recognize that continuing to smoke exposes them to greater health risks and are willing to undergo lung cancer screening and receive pneumococcal vaccines, a kind of fatalism frequently sets in. I’ve heard more times than I can recall some version of the declaration, “It’s too late for quitting to make much difference for me.” Many smokers think that once they reach middle age, gains in life expectancy will be too small to be worth the intense effort and multiple failed attempts that are typically required to quit permanently. Until recently, there were few data I could call on to persuade them they were wrong.

In February 2024, Dr. Eo Rin Cho and colleagues pooled data from four national cohort studies (United States, United Kingdom, Norway, and Canada) to calculate mortality differences among current, former, and never smokers aged 20-79 years. Compared with never smokers, lifelong smokers died an average of 12-13 years earlier. However, quitting before age 50 nearly eliminated the excess mortality associated with smoking, and in the 50- to 59-year-old age group, cessation eventually reduced excess mortality by 92%-95%. Better yet, more than half of the benefits occurred within the first 3 years after cessation.

At first glance, these estimates may seem too good to be true. A few months later, though, a different research group, using data from a large cancer prevention study and 2018 US population census and mortality rates, largely confirmed their findings. Dr. Thuy Le and colleagues found that quitting at age 35, 45, 55, 65, or 75 years resulted in average life gains of 8, 5.6, 3.5, 1.7, and 0.7 years, respectively, relative to continuing to smoke. Because no patient is average, the analysis also presented some helpful probabilities. For example, a smoker who quits at age 65 has about a 1 in 4 chance of gaining at least 1 full year of life and a 1 in 6 chance of gaining at least 4 years. In other words, from a life expectancy perspective alone, it’s almost never too late to quit smoking.

Dr. Lin is a family physician and Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor. He has disclosed no relevant financial relationships.

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

An estimated 450,000 US deaths are expected this year from conditions attributed to cigarette smoking. Although the percentage of adults who smoke declined from 21% in 2005 to 11% in 2022, the annual death toll has been stable since 2005 and isn’t expected to decline until 2030, owing to an aging population of current and former smokers.

In 2022, based on a national survey, two thirds of the 28.8 million US adult smokers wanted to quit, and more than half tried quitting on their own or with the help of clinicians, but less than 9% succeeded in kicking the habit. The health benefits of quitting, summarized in a patient education handout from the American Cancer Society, include a lower risk for cancer, diabetes, and cardiovascular disease. Furthermore, the handout states, “quitting smoking can add as much as 10 years to your life, compared to if you continued to smoke.”

For my patients older than age 50 who are lifelong smokers, the qualifier “as much as” can be a sticking point. Although most recognize that continuing to smoke exposes them to greater health risks and are willing to undergo lung cancer screening and receive pneumococcal vaccines, a kind of fatalism frequently sets in. I’ve heard more times than I can recall some version of the declaration, “It’s too late for quitting to make much difference for me.” Many smokers think that once they reach middle age, gains in life expectancy will be too small to be worth the intense effort and multiple failed attempts that are typically required to quit permanently. Until recently, there were few data I could call on to persuade them they were wrong.

In February 2024, Dr. Eo Rin Cho and colleagues pooled data from four national cohort studies (United States, United Kingdom, Norway, and Canada) to calculate mortality differences among current, former, and never smokers aged 20-79 years. Compared with never smokers, lifelong smokers died an average of 12-13 years earlier. However, quitting before age 50 nearly eliminated the excess mortality associated with smoking, and in the 50- to 59-year-old age group, cessation eventually reduced excess mortality by 92%-95%. Better yet, more than half of the benefits occurred within the first 3 years after cessation.

At first glance, these estimates may seem too good to be true. A few months later, though, a different research group, using data from a large cancer prevention study and 2018 US population census and mortality rates, largely confirmed their findings. Dr. Thuy Le and colleagues found that quitting at age 35, 45, 55, 65, or 75 years resulted in average life gains of 8, 5.6, 3.5, 1.7, and 0.7 years, respectively, relative to continuing to smoke. Because no patient is average, the analysis also presented some helpful probabilities. For example, a smoker who quits at age 65 has about a 1 in 4 chance of gaining at least 1 full year of life and a 1 in 6 chance of gaining at least 4 years. In other words, from a life expectancy perspective alone, it’s almost never too late to quit smoking.

Dr. Lin is a family physician and Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor. He has disclosed no relevant financial relationships.

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

An estimated 450,000 US deaths are expected this year from conditions attributed to cigarette smoking. Although the percentage of adults who smoke declined from 21% in 2005 to 11% in 2022, the annual death toll has been stable since 2005 and isn’t expected to decline until 2030, owing to an aging population of current and former smokers.

In 2022, based on a national survey, two thirds of the 28.8 million US adult smokers wanted to quit, and more than half tried quitting on their own or with the help of clinicians, but less than 9% succeeded in kicking the habit. The health benefits of quitting, summarized in a patient education handout from the American Cancer Society, include a lower risk for cancer, diabetes, and cardiovascular disease. Furthermore, the handout states, “quitting smoking can add as much as 10 years to your life, compared to if you continued to smoke.”

For my patients older than age 50 who are lifelong smokers, the qualifier “as much as” can be a sticking point. Although most recognize that continuing to smoke exposes them to greater health risks and are willing to undergo lung cancer screening and receive pneumococcal vaccines, a kind of fatalism frequently sets in. I’ve heard more times than I can recall some version of the declaration, “It’s too late for quitting to make much difference for me.” Many smokers think that once they reach middle age, gains in life expectancy will be too small to be worth the intense effort and multiple failed attempts that are typically required to quit permanently. Until recently, there were few data I could call on to persuade them they were wrong.

In February 2024, Dr. Eo Rin Cho and colleagues pooled data from four national cohort studies (United States, United Kingdom, Norway, and Canada) to calculate mortality differences among current, former, and never smokers aged 20-79 years. Compared with never smokers, lifelong smokers died an average of 12-13 years earlier. However, quitting before age 50 nearly eliminated the excess mortality associated with smoking, and in the 50- to 59-year-old age group, cessation eventually reduced excess mortality by 92%-95%. Better yet, more than half of the benefits occurred within the first 3 years after cessation.

At first glance, these estimates may seem too good to be true. A few months later, though, a different research group, using data from a large cancer prevention study and 2018 US population census and mortality rates, largely confirmed their findings. Dr. Thuy Le and colleagues found that quitting at age 35, 45, 55, 65, or 75 years resulted in average life gains of 8, 5.6, 3.5, 1.7, and 0.7 years, respectively, relative to continuing to smoke. Because no patient is average, the analysis also presented some helpful probabilities. For example, a smoker who quits at age 65 has about a 1 in 4 chance of gaining at least 1 full year of life and a 1 in 6 chance of gaining at least 4 years. In other words, from a life expectancy perspective alone, it’s almost never too late to quit smoking.

Dr. Lin is a family physician and Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He blogs at Common Sense Family Doctor. He has disclosed no relevant financial relationships.

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.

TOPLINE:

Among patients with overweight or obesity, frontline immunotherapy for advanced non–small cell lung cancer (NSCLC) was not associated with a survival benefit compared with conventional chemotherapy. Overall, however, compared with low body mass index (BMI), overweight or obesity was associated with a lower risk for mortality among patients receiving either therapy.

METHODOLOGY:

• The association between BMI and overall survival in patients with cancer who receive immunotherapy or conventional chemotherapy in the frontline remains unclear. Patients with cancer and obesity are generally considered to have a worse prognosis, but some data suggest an obesity paradox, where patients with cancer and a higher BMI demonstrate better overall survival following immunotherapy or chemotherapy.
• To clarify whether (or how) BMI affects overall survival outcomes and the optimal frontline treatment choice, researchers evaluated 31,257 patients with advanced NSCLC from Japan who received immune checkpoint inhibitors (n = 12,816) or conventional chemotherapy (n = 18,441).
• Patient outcomes were assessed according to weight categories and frontline therapy type (immune checkpoint inhibitors or conventional chemotherapy), with overall survival as the primary outcome.
• A BMI < 18.5 was considered underweight, 18.5-24.9 was considered normal weight, 25.0-29.9 was considered overweight, and ≥ 30.0 was considered obese.

TAKEAWAY:

• In the overall population, regardless of weight, patients who received chemotherapy had a higher mortality rate than those who received immunotherapy — 35.9% vs 28.0%, respectively — over a follow-up of 3 years.
• However, overweight or obesity was associated with a lower risk for mortality compared with a lower BMI among patients with advanced NSCLC, regardless of whether they received immune checkpoint inhibitor therapy or conventional chemotherapy.
• Among patients who received immunotherapy, the risk for mortality decreased steadily as BMI increased from 15 to 24 and then increased at higher BMIs, indicating a U-shaped association.
• Immunotherapy was associated with a significant improvement in overall survival compared with conventional chemotherapy among patients with a BMI < 28; however, researchers observed no difference in overall survival between the two therapies in those with a BMI ≥ 28.

IN PRACTICE:

Overall, “these results support the presence of the obesity paradox in patients with [advanced] NSCLC who underwent either therapy,” the authors concluded.

But when focused on patients in the higher BMI group, there was no overall survival benefit with the frontline immunotherapy vs the conventional chemotherapy. “Immunotherapy therapy may not necessarily be the optimal first-line therapy for patients with overweight or obesity,” the authors wrote, adding that “the use of conventional chemotherapy should also be considered.”

SOURCE:

The study, led by Yasutaka Ihara, PharmD, Osaka Metropolitan University, Osaka, Japan, was published online in JAMA Network Open.

LIMITATIONS: 

Retrospective design has inherent bias. PD-L1 status was not known, and the inclusion of Japanese population may have limited the generalizability of the findings. 

DISCLOSURES:

This study received funding from the Graduate School of Medicine, Osaka Metropolitan University. Several authors reported receiving personal fees from various pharmaceutical sources.

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:

Among patients with overweight or obesity, frontline immunotherapy for advanced non–small cell lung cancer (NSCLC) was not associated with a survival benefit compared with conventional chemotherapy. Overall, however, compared with low body mass index (BMI), overweight or obesity was associated with a lower risk for mortality among patients receiving either therapy.

METHODOLOGY:

• The association between BMI and overall survival in patients with cancer who receive immunotherapy or conventional chemotherapy in the frontline remains unclear. Patients with cancer and obesity are generally considered to have a worse prognosis, but some data suggest an obesity paradox, where patients with cancer and a higher BMI demonstrate better overall survival following immunotherapy or chemotherapy.
• To clarify whether (or how) BMI affects overall survival outcomes and the optimal frontline treatment choice, researchers evaluated 31,257 patients with advanced NSCLC from Japan who received immune checkpoint inhibitors (n = 12,816) or conventional chemotherapy (n = 18,441).
• Patient outcomes were assessed according to weight categories and frontline therapy type (immune checkpoint inhibitors or conventional chemotherapy), with overall survival as the primary outcome.
• A BMI < 18.5 was considered underweight, 18.5-24.9 was considered normal weight, 25.0-29.9 was considered overweight, and ≥ 30.0 was considered obese.

TAKEAWAY:

• In the overall population, regardless of weight, patients who received chemotherapy had a higher mortality rate than those who received immunotherapy — 35.9% vs 28.0%, respectively — over a follow-up of 3 years.
• However, overweight or obesity was associated with a lower risk for mortality compared with a lower BMI among patients with advanced NSCLC, regardless of whether they received immune checkpoint inhibitor therapy or conventional chemotherapy.
• Among patients who received immunotherapy, the risk for mortality decreased steadily as BMI increased from 15 to 24 and then increased at higher BMIs, indicating a U-shaped association.
• Immunotherapy was associated with a significant improvement in overall survival compared with conventional chemotherapy among patients with a BMI < 28; however, researchers observed no difference in overall survival between the two therapies in those with a BMI ≥ 28.

IN PRACTICE:

Overall, “these results support the presence of the obesity paradox in patients with [advanced] NSCLC who underwent either therapy,” the authors concluded.

But when focused on patients in the higher BMI group, there was no overall survival benefit with the frontline immunotherapy vs the conventional chemotherapy. “Immunotherapy therapy may not necessarily be the optimal first-line therapy for patients with overweight or obesity,” the authors wrote, adding that “the use of conventional chemotherapy should also be considered.”

SOURCE:

The study, led by Yasutaka Ihara, PharmD, Osaka Metropolitan University, Osaka, Japan, was published online in JAMA Network Open.

LIMITATIONS: 

Retrospective design has inherent bias. PD-L1 status was not known, and the inclusion of Japanese population may have limited the generalizability of the findings. 

DISCLOSURES:

This study received funding from the Graduate School of Medicine, Osaka Metropolitan University. Several authors reported receiving personal fees from various pharmaceutical sources.

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:

Among patients with overweight or obesity, frontline immunotherapy for advanced non–small cell lung cancer (NSCLC) was not associated with a survival benefit compared with conventional chemotherapy. Overall, however, compared with low body mass index (BMI), overweight or obesity was associated with a lower risk for mortality among patients receiving either therapy.

METHODOLOGY:

• The association between BMI and overall survival in patients with cancer who receive immunotherapy or conventional chemotherapy in the frontline remains unclear. Patients with cancer and obesity are generally considered to have a worse prognosis, but some data suggest an obesity paradox, where patients with cancer and a higher BMI demonstrate better overall survival following immunotherapy or chemotherapy.
• To clarify whether (or how) BMI affects overall survival outcomes and the optimal frontline treatment choice, researchers evaluated 31,257 patients with advanced NSCLC from Japan who received immune checkpoint inhibitors (n = 12,816) or conventional chemotherapy (n = 18,441).
• Patient outcomes were assessed according to weight categories and frontline therapy type (immune checkpoint inhibitors or conventional chemotherapy), with overall survival as the primary outcome.
• A BMI < 18.5 was considered underweight, 18.5-24.9 was considered normal weight, 25.0-29.9 was considered overweight, and ≥ 30.0 was considered obese.

TAKEAWAY:

• In the overall population, regardless of weight, patients who received chemotherapy had a higher mortality rate than those who received immunotherapy — 35.9% vs 28.0%, respectively — over a follow-up of 3 years.
• However, overweight or obesity was associated with a lower risk for mortality compared with a lower BMI among patients with advanced NSCLC, regardless of whether they received immune checkpoint inhibitor therapy or conventional chemotherapy.
• Among patients who received immunotherapy, the risk for mortality decreased steadily as BMI increased from 15 to 24 and then increased at higher BMIs, indicating a U-shaped association.
• Immunotherapy was associated with a significant improvement in overall survival compared with conventional chemotherapy among patients with a BMI < 28; however, researchers observed no difference in overall survival between the two therapies in those with a BMI ≥ 28.

IN PRACTICE:

Overall, “these results support the presence of the obesity paradox in patients with [advanced] NSCLC who underwent either therapy,” the authors concluded.

But when focused on patients in the higher BMI group, there was no overall survival benefit with the frontline immunotherapy vs the conventional chemotherapy. “Immunotherapy therapy may not necessarily be the optimal first-line therapy for patients with overweight or obesity,” the authors wrote, adding that “the use of conventional chemotherapy should also be considered.”

SOURCE:

The study, led by Yasutaka Ihara, PharmD, Osaka Metropolitan University, Osaka, Japan, was published online in JAMA Network Open.

LIMITATIONS: 

Retrospective design has inherent bias. PD-L1 status was not known, and the inclusion of Japanese population may have limited the generalizability of the findings. 

DISCLOSURES:

This study received funding from the Graduate School of Medicine, Osaka Metropolitan University. Several authors reported receiving personal fees from various pharmaceutical sources.

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.

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.

The US Food and Drug Administration (FDA) has approved afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) to treat advanced synovial sarcoma. 

Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.

The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.

Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities. 

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”

T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors. 

The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew. 

According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.

“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.

The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.

The list price for the one-time therapy is $727,000, according to Fierce Pharma.
 

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

The US Food and Drug Administration (FDA) has approved afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) to treat advanced synovial sarcoma. 

Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.

The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.

Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities. 

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”

T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors. 

The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew. 

According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.

“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.

The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.

The list price for the one-time therapy is $727,000, according to Fierce Pharma.
 

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

The US Food and Drug Administration (FDA) has approved afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) to treat advanced synovial sarcoma. 

Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.

The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.

Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities. 

“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”

T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors. 

The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew. 

According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.

“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.

The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.

The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.

The list price for the one-time therapy is $727,000, according to Fierce Pharma.
 

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