Second-line treatment strategies and clinical outcomes after progression on chemoimmunotherapy in extensive-stage small-cell lung cancer.

Background In extensive-stage small cell lung cancer (ES-SCLC), chemoimmunotherapy (CIO) is the standard first-line (1L). However, real-world data describing second-line (2L) outcomes post-CIO remain limited. We assessed 2L outcomes following progression after 1L CIO. Methods We analyzed retrospective multicenter patient data from the AUstralasian thoRacic cancers lOngitudinal cohoRt study and biobAnk (AURORA). Population characteristics and treatment outcomes were summarized using descriptive statistics. Survival was estimated using the Kaplan-Meier method; covariate effects were evaluated using Cox proportional hazards models. Results We included 111 patients from 10 Australian centers. Median age was 65 years (Q1-Q3: 58-72); 58 % male, 96 % current or former smokers, and 74 % had ECOG ≤ 1. Patients received a median of 8 CIO cycles (97 % atezolizumab) before 2L treatment. Common 2L regimens included lurbinectedin (32 %), carboplatin/etoposide rechallenge (21 %), CAV (20 %), and topotecan (9 %). Platinum-sensitive relapse (≥6-month chemotherapy-free interval) occurred in 27 %. Among rechallenge patients, the median interval from 1L to 2L platinum was 192 days (Q1-Q3: 155-308). The 2L objective response rate was 22 %. Median duration of response was 2.2 months (95 % CI: 1.8-3.3), progression-free survival 2.9 months (95 % CI: 2.5-3.5), and overall survival 5.8 months (95 % CI: 4.6-6.4). Rechallenge with carboplatin/etoposide was associated with numerically longer survival compared to other 2L agents. No significant differences in PFS or OS were observed among non-rechallenge regimens. Conclusion 2L survival outcomes post-CIO were similar to historical results after chemotherapy alone. Despite 1L immunotherapy, 2L response rates and survival remain poor, underscoring the need for more effective strategies in ES-SCLC.