Older adults with extensive-stage small-cell lung cancer treated with first-line chemoimmunotherapy: Updated systematic review and meta-analysis.

Abstract

e20152 Background: Small-cell lung cancer (SCLC) accounts for ~10–15% of lung cancers, and most patients present with extensive-stage disease (ES-SCLC) with poor survival. PD-1/PD-L1 immune checkpoint inhibitors (ICIs) added to first-line platinum-etoposide have changed standard care, but older adults (≥70 years) remain underrepresented despite forming a large real-world ES-SCLC population. With newer data and longer follow-up now available, we updated prior evidence to better define outcomes in older patients treated with ICI–chemotherapy. Methods: Following PRISMA principles, we searched multiple electronic databases from inception through January 5 for randomized trials of first-line platinum–etoposide with vs without PD-1/PD-L1 ICIs. The most mature report per trial was used. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Random-effects meta-analysis pooled hazard ratios (HRs) with heterogeneity assessed by I²/τ²; funnel plots and leave-one-out analyses. Results: Ten studies contributed OS. ICI–chemotherapy significantly improved OS versus control (HR 0.79, 95% CI 0.71–0.89), with moderate heterogeneity (I² 31.8%, τ² 0.0096; p = 0.154) and a prediction interval of 0.61–1.02. Four studies contributed PFS, demonstrating improved PFS (HR 0.67, 95% CI 0.60–0.74) with low heterogeneity (I² 10.4%, τ² 0.0013; p = 0.341) and a prediction interval of 0.54–0.82. Leave-one-out analyses showed stable effects, and funnel plots did not suggest major small-study effects. Conclusions: In updated randomized evidence, adding PD-1/PD-L1 ICIs to first-line platinum- etoposide provides clinically meaningful improvements in both OS and PFS, with low-to-moderate heterogeneity. These findings support continued use in older adults while emphasizing the need for better age-stratified reporting and dedicated studies to refine patient selection.