Immunotherapy maintenance in extensive-stage small-cell lung cancer: a real-world retrospective study

Although immune checkpoint inhibitors (ICIs) are commonly continued as maintenance therapy after induction for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor and real-world evidence specifically evaluating post-induction maintenance immunotherapy is limited. This study aimed to evaluate the association between post-induction maintenance immunotherapy and survival outcomes in patients with ES-SCLC treated with first-line chemoimmunotherapy.

This multicenter retrospective cohort study included 263 patients with ES-SCLC who received first-line platinum-etoposide chemotherapy plus an ICI. Primary analyses were performed in a landmark cohort of patients alive and progression-free after induction chemoimmunotherapy to reduce immortal-time and guarantee-time bias. Landmark-defined overall survival (OS) and progression-free survival (PFS) were compared between maintenance and non-maintenance groups using Kaplan-Meier analysis and treatment-adjusted Cox models. Inverse probability of treatment weighting (IPTW), propensity score matching (PSM), and an actual/pseudo-index date analysis were performed as sensitivity analyses.

The landmark cohort included 235 patients (128 maintenance, 107 non-maintenance). Maintenance immunotherapy was associated with longer landmark-defined OS (median, 370 vs. 243 days; P<0.01) and PFS (median, 209 vs. 124 days; P<0.01). In adjusted Cox models, maintenance remained associated with improved OS [hazard ratio (HR) =0.70; 95% confidence interval (CI): 0.50-0.97] and PFS (HR =0.70; 95% CI: 0.52-0.92). IPTW analyses yielded similar estimates for OS (HR =0.71; 95% CI: 0.51-0.98) and PFS (HR =0.69; 95% CI: 0.52-0.91). PSM analyses were exploratory and showed attenuated, non-significant estimates. In the actual/pseudo-index analysis (174 patients), maintenance remained associated with OS (HR =0.49; 95% CI: 0.30-0.78), whereas the PFS estimate was attenuated and non-significant (HR =0.71; 95% CI: 0.47-1.05; P=0.089).

These findings provide hypothesis-generating real-world evidence supporting further prospective evaluation of maintenance immunotherapy as a post-induction strategy in selected patients with ES-SCLC.