In the treatment of extensive-stage small-cell lung cancer (ES-SCLC), adding PD-1 or PD-L1 inhibitors to platinum-etoposide in the first line consistently improves survival outcomes, according to research published in Lung Cancer.
No difference in survival benefit is seen between PD-1 inhibitors and PD-L1 inhibitors, study researchers reported.
In this meta-analysis, the researchers searched MEDLINE, Scopus, and Cochrane CENTRAL through February 11, 2026, for phase 3 randomized controlled trials that enrolled adults with previously untreated ES-SCLC. Eligible studies compared platinum-etoposide chemotherapy plus a PD-1/PD-L1 inhibitor to platinum-etoposide alone. Ultimately, 6 trials comprising 2897 patients were included in the analysis.
When the researchers examined the studies individually, they found that overall survival (OS) in all of them favored the combination of a PD-1/PD-L1 inhibitor with platinum-etoposide over platinum-etoposide alone, with hazard ratios (HRs) ranging from 0.63 to 0.80. The same was true for progression-free survival (PFS; HR range, 0.48-0.78).
When the results from the 6 trials were synthesized in a random effects model, the pooled OS estimate also favored PD-1/PD-L1 inhibitor plus platinum-etoposide over platinum-etoposide alone (HR, 0.735; 95% CI, 0.671-0.805; P <.0001 wp_automatic_readability="19">
Likewise, the pooled PFS estimate favored PD-1/PD-L1 inhibitor plus platinum-etoposide over platinum-etoposide alone (HR, 0.675; 95% CI, 0.585-0.780; P <.0001 wp_automatic_readability="29">
There was no significant difference between PD-1 inhibitors and PD-L1 inhibitors in terms of either OS (HR, 1.01; 95% CI, 0.849-1.21; P =.892) or PFS (HR, 0.834; 95% CI, 0.638-1.09; P =.184).
In addition, the researchers reported that there was no significant increase in grade 3 or higher adverse events with the addition of PD-1/PD-L1 inhibitors to platinum-etoposide.
“On the other hand, immune-mediated adverse events were more frequent in the experimental cohorts, consistent with the mechanism of immune checkpoint inhibition, but were characterized by substantial heterogeneity across studies and wide prediction intervals,” the researchers wrote.
“Adding a PD-1/PD-L1 inhibitor to platinum-etoposide in first-line ES-SCLC provides a consistent overall survival benefit, with no statistically detectable differences between PD-1 and PD-L1 inhibitor classes,” the researchers concluded. “This finding should be interpreted as absence of detectable class-level divergence rather than pharmacologic equivalence.”
Disclosures: There was no funding for this study. The study authors reported having no conflicts of interest. Please see the original reference for complete disclosures.
References:
Lamberti G, Andrini E, Zappi A, Di Odoardo A, Formelli M.G., Campana D. Phase III meta-analysis of first-line chemo-immunotherapy in ES-SCLC: Survival benefit without detectable class-level differences. Lung Cancer. Published online March 17, 2026. doi:10.1016/j.lungcan.2026.109376.
