Immunotherapy improves survival in ES-SCLC in first-line setting

First-line treatment with immune checkpoint inhibitors (ICIs) is safe and effective in patients with extended stage (ES) small-cell lung cancer (SCLC), but its use as second-line agent is not recommended, according to a study.

The authors searched the databases of PubMed, Embase, and Cochrane Library between January 2010 and March 2025 and conference proceedings between 2018 and 2025 for randomized controlled trials investigating ICIs vs chemotherapy in patients with ES-SCLC.

Overall survival (OS) and progression-free survival (PFS) were the primary endpoints, while objective response rate (ORR) and grade 3+ adverse events were secondary. The generic inverse variance method was used for the meta-analysis of pooled hazard ratios (HRs) for OS and PFS. Pooled estimates were calculated using random-effect models.

Finally, the authors performed subgroups analyses to compare survival by line of therapy, sex, age, and ECOG status.

The use of ICIs resulted in a 19-percent lower risk of mortality (HR, 0.81, 95 percent confidence interval [CI], 0.76‒0.86). OS benefit was achieved regardless of age, sex, or ECOG, but only in the first-line setting. Similarly, ICIs reduced the risk of disease progression by 22 percent (HR, 0.78, 95 percent CI, 0.67‒0.91), with PFS benefit restricted to first-line treatment and a detrimental effect in the second-line setting.

For the secondary endpoints, ICIs improved ORR (odds ratio [OR], 0.79, 95 percent CI, 0.66‒0.95) but appeared to contribute to increased grade 3+ diarrhoea (OR, 3.63, 95 percent CI, 1.46‒9.02).

“Biomarkers predicting long-term benefit are needed to further improve outcomes,” the authors said.