In a study reported in JAMA Oncology, Heyward et al examined the harm-benefit balance of immune checkpoint inhibitor use across lines of treatment in non–small cell lung cancer (NSCLC).
Study Details
The retrospective cohort study, conducted in 2024, involved 2013 to 2019 Surveillance, Epidemiology, and End Results–Medicare data on patents aged 66 years or older with NSCLC who were exposed to immune checkpoint inhibitor plus chemotherapy or immune checkpoint inhibitor alone. Severe immune-related adverse events constituted harm, and delayed mortality constituted benefit. Analysis included immune checkpoint inhibitor use in the first or second or later line of systemic anticancer treatment. The harm-benefit tradeoff was calculated as excess severe immune-related adverse events per year of life gained in which the gain in survival time was assessed using restricted mean survival time.
Key Findings
Among the 17,681 Medicare beneficiaries included in the analysis, 49.5% were female, and the mean patient age was 74 ± 6.0 years. Compared with patients receiving a single immune checkpoint inhibitor (80.6%), those receiving an immune checkpoint inhibitor plus chemotherapy (19.4%) had a significant elevated risk of severe immune-related adverse events in the first setting of systemic anticancer treatment (hazard ratio [HR] = 1.18, 95% confidence interval [CI] = 1.06–1.30) but no significant elevated risk in the second or later lines of systemic anticancer treatment (HR = 1.04, 95% CI = 0.92–1.19).
Patients receiving an immune checkpoint inhibitor plus chemotherapy had a significantly lower risk of mortality vs single immune checkpoint inhibitor in the first setting of systemic anticancer treatment (HR = 0.66, 95% CI, 0.61–0.73) but not in the second or later line of systemic anticancer treatment (HR = 0.94, 95% CI = 0.80–1.10).
A significant tradeoff between harms and benefits for immune checkpoint inhibitor plus chemotherapy vs immune checkpoint inhibitor alone was observed in the first line of systemic anticancer treatment: each year of additional survival associated with an immune checkpoint inhibitor plus chemotherapy was accompanied by 0.31 additional severe immune-related adverse events (excess severe immune-related adverse events per year of life gained; HR = 0.31, 95% CI = 0.06–0.52). In the first line of systemic anticancer treatment, an immune checkpoint inhibitor plus chemotherapy delayed mortality more among patients with vs without autoimmune disease at baseline (HR = 0.51, 95% CI = 0.39–0.67).
The investigators concluded: “The results of this cohort study suggest that given both treatment-related harms and benefits, [immune checkpoint inhibitor plus] chemotherapy use in the first [systemic anticancer treatment] setting requires informed decision-making; the potential benefits of [immune checkpoint inhibitor plus] chemotherapy vs single [immune checkpoint inhibitor] in high-risk subgroups are encouraging.”
Jodi B. Segal, MD, MPH, of Johns Hopkins University, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Institute on Aging, National Heart, Lung and Blood Institute, National Cancer Institute, and others. For full disclosures of all study authors, visit JAMA Oncology.
