Lurbinectedin versus platinum rechallenge in relapsed extensive stage small cell lung cancer: A retrospective cohort study.

e20110 Background: Outcomes in small cell lung cancer (SCLC) remain exceptionally poor. Although patients typically have an excellent initial response to platinum doublet chemotherapy, relapse occurs quickly. Despite multiple available therapeutic options for patients with relapse after first-line treatment, there remains limited evidence indicating a preferred second-line therapy. We present findings from a retrospective cohort study comparing lurbinectedin with platinum rechallenge in a real-world setting. Methods: Patient records were identified from Vanderbilt Ingram Cancer Center between 2000 and 2023. The study cohort included extensive-stage (ES) SCLC patients treated with second-linelurbinectedin or platinum rechallenge following initial platinum-based chemotherapy.Primary outcomes included overall survival (OS) and progression-free survival (PFS). Secondary outcomes were drug-related adverse events including hospitalization, neutropenic fever, and laboratory abnormalities by CTCAE definitions. Analysis was done in R using Kaplan-Meier estimates and Cox proportional hazards models. Results: 57 patients met inclusion criteria, with 21 receiving lurbinectedin and 36 receiving platinum rechallenge. Cohorts were similar for sex, race, comorbidities, and performance status. The platinum rechallenge group skewed younger with longer chemotherapy-free interval (CTFI) (median 9.71 months vs. 2.59 months for lurbinectedin). Median PFS was 4.37 (1.53, 5.94) vs. 2.63 months (1.68, 4.40) (p = 0.030) and median OS was 8.61 (4.91, 14.26) vs. 4.70 months (2.63, 6.73) (p = 0.001) for platinum rechallenge and lurbinectedin, respectively. In a Cox proportional hazard analysis, OS and PFS hazard ratios for lurbinectedin compared to platinum rechallenge were 4.43 (1.89-10.4, p < 0.001) and 2.03 (0.87-4.8) (p = 0.102) after adjusting for age, sex, race, comorbidities, and CTFI. Notably, the OS and PFS hazard ratios for CTFI alone were 0.96 (0.9-1.0) and 0.99 (0.98-1.0). There was no statistically significant difference in hospitalizations, neutropenic fever, anemia, or transaminitis between groups, although 7 (29%) of platinum rechallenge patients discontinued due to tolerability compared to 0 (0%) with lurbinectedin. Conclusions: This retrospective cohort study suggests that second-line platinum rechallenge in patients with relapsed ES-SCLC may be associated with improved OS and PFS compared to lurbinectedin. While time since last platinum was notably different between cohorts, CTFI alone did not appear to explain the observed difference in outcomes. Drug-related safety events were similar, although tolerability led to greater discontinuation with platinum chemotherapy. Although a small, single-center retrospective study, these results support further research to identify an optimal therapeutic strategy in second-line treatment of ES-SCLC.