Rethinking the Platinum Standard in SCLC: A Meta-Analysis of Limited- and Extensive-Stage Disease in the Immunotherapy Era.

INTRODUCTION

SCLC is an aggressive malignancy for which platinum-based chemotherapy is the cornerstone of treatment. Although immunotherapy has redefined the standard of care, the optimal choice between cisplatin and carboplatin remains debated. This study evaluated the impact of platinum backbone selection on survival outcomes across the SCLC spectrum in the immunotherapy era.

METHODS

A systematic review and meta-analysis were performed on randomized controlled trials evaluating first-line chemoimmunotherapy with platinum-based regimens in SCLC. Outcomes were stratified by disease stage and platinum backbone (carboplatin versus cisplatin). Survival end points included progression-free survival (PFS) and overall survival (OS).

RESULTS

Seven trials (3059 patients) were analyzed. In extensive-stage SCLC (n = 1843), both backbones provided comparable benefits when combined with immunotherapy; the pooled OS hazard ratio (HR) for cisplatin was 0.71 (95% confidence interval [CI]: 0.57-0.89; p = 0.003) and 0.76 for carboplatin (95% CI: 0.68-0.85; p < 0.001). In limited-stage SCLC (n = 1216), the addition of immunotherapy improved OS (HR: 0.71; 95% CI: 0.54-0.92; p = 0.01) and PFS (HR: 0.70; 95% CI: 0.56-0.87; p = 0.002) in carboplatin-treated patients, whereas, in cisplatin-treated patients the benefit did not reach statistical significance for OS (HR: 1.15; 95% CI: 0.77-1.72; p = 0.49) or PFS (HR: 1.02; 95% CI: 0.81-1.28; p = 0.87).

CONCLUSION

These findings invite a reconsideration of the platinum hierarchy in SCLC management. By demonstrating that carboplatin provides a more effective backbone in the limited-stage setting and comparable efficacy in the extensive-stage setting, this analysis suggests that the historical prioritization of cisplatin may no longer be justified in the era of immunotherapy. Prioritizing carboplatin as a preferred agent may optimize tolerability while preserving or improving survival outcomes across the SCLC spectrum.