Rechallenge With Immunotherapy for ES-SCLC: Efficacy and Safety From a Retrospective Propensity Score-Matched Study

Although immunotherapy combined with platinum-based chemotherapy is now the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), the benefit of continuing immune checkpoint inhibitors (ICIs) after disease progression (PD) remains uncertain. This real-world study assessed the efficacy and safety of second-line immunotherapy in ES-SCLC patients using propensity score matching (PSM).

ES-SCLC patients who received second-line treatments following first-line chemoimmunotherapy at Zhejiang Cancer Hospital from January 2019 to December 2023 were included. Clinical baseline characteristics were collected and balanced. The efficacy and safety of patients who continued to receive second-line immunotherapy were compared with those who did not.

A total of 187 patients were analyzed. The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 8.5 months (95% CI: 7.1-9.9) and 3.3 months (95% CI: 2.5-4.1), respectively. After PSM, each group included 76 patients. No significant differences in OS (median OS: 8.3 vs. 7.8 months; HR, 0.97; 95% CI: 0.68-1.39; p = 0.87) or PFS (median PFS: 3.45 vs. 3.1 months; HR, 1.07; 95% CI: 0.77-1.49; p = 0.69) were observed between the rechallenge and non-rechallenge groups. Subgroup analysis suggested in an exploratory manner that immunotherapy rechallenge was associated with poorer outcomes in non-smokers (mOS: 8 vs. 16.6 months; HR, 2.9; 95% CI: 1.1-7.9; p = 0.004). The rate of all-grade immune-related adverse events (irAEs) was higher in the rechallenge group (36.8% vs. 17.1%).

Rechallenge with immunotherapy after first-line chemoimmunotherapy may not demonstrate a significant survival benefit in ES-SCLC patients, particularly among never smokers, and may lead to more frequent irAEs.