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TOPLINE:

Immunotherapy plus chemotherapy — the standard treatment for non–small cell lung cancer (NSCLC) — does not confer survival benefits over immunotherapy alone but does increase the side-effect burden in older patients.

METHODOLOGY:

• Clinical trials have shown that combining immunotherapy and chemotherapy leads to longer overall survival in patients with NSCLC, but these trials often excluded older patients.
• This retrospective study assessed the potential benefits of an immunotherapy-chemotherapy combination in 1245 older patients (median age, 78 years; 78% men) with previously untreated advanced NSCLC recruited from 58 centers in Japan.
• Programmed death ligand-1 (PD-L1) expression < 1%, 1%-49%, and ≥ 50% was noted in 22%, 31%, and 33% of tumors, respectively. PD-L1 expression was unknown in 14% of tumors.
• Overall, 28% of patients received immunotherapy combined with chemotherapy, 34% received only immunotherapy, 25% received platinum-doublet chemotherapy, and 12% received single-agent chemotherapy. Pembrolizumab monotherapy was the most frequent immunotherapy used.
• Overall survival, progression-free survival, and safety were the main outcomes.

TAKEAWAY:

• After a median follow-up of 19.2 months, the median overall survival was similar in the two study arms, at 20.0 months in the combination group and 19.8 months in the immunotherapy alone group; progression-free survival was 7.7 months in both groups.
• Compared with immunotherapy alone, immunotherapy plus chemotherapy did not improve overall survival or progression-free survival in patients grouped by PD-L1 expression.
• However, immunotherapy plus chemotherapy increased the incidence of grade 3 or higher immune-related adverse events compared with immunotherapy alone (24.3% vs 17.9%; P = .03).
• A greater proportion of patients also required steroids to treat immune-related adverse events in the immunotherapy plus chemotherapy group (32.5% vs 24.7% for immunotherapy alone; P = .02).

IN PRACTICE:

Based on these findings, an immune checkpoint inhibitor alone "may be recommended for older adult patients with PD-L1–positive NSCLC," the authors wrote.

In an accompanying editorial, Elad Sharon, MD, MPH, from Dana-Farber Cancer Institute, Boston, Massachusetts, suggested the results should be approached with caution, noting that although the study shows "chemotherapy and immunotherapy have similar numerical outcomes when compared with immunotherapy alone, the question becomes which chemotherapy and for which patients?"

SOURCE:

Yoko Tsukita, MD, PhD, Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, led this study, which was published online on March 7, 2024, in JAMA Oncology.

LIMITATIONS:

The tumor assessment timing may have been different across different study sites owing to the retrospective nature of this study. The attending physician did not resort to a central review before determining whether an adverse event was immune-related. All the patients enrolled in this study were of Japanese ethnicity.

DISCLOSURES:

The authors declared receiving personal fees from various pharmaceutical companies, including AstraZeneca, Chugai Pharmaceutical, and Bristol-Meyers Squib.