Lurbinectedin plus atezolizumab vs durvalumab maintenance in ES-SCLC: A comparative clinical and economic analysis

Background Extensive-stage small cell lung cancer (ES-SCLC) treatment has evolved with improving survival with addition of immunotherapy treatment. Recently, the IMforte trial reported better survival outcomes by adding lurbectindin maintenance with atezolizumab after induction therapy. This approach challenges the current widely used durvalumab-based regimen (CASPIAN trial) for treatment of ES-SCLC. We aim to analyze the survival outcomes, toxicity, tolerability, and cost-effectiveness of these regimens. Methods: Data from IMforte and CASPIAN trials were directly extracted from published primary manuscripts and associated supplementary materials and synthesized descriptively. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were analyzed from trial data. Adverse events (AEs), tolerability, and cost-effectiveness using the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) were compared. Results: In IMforte maintenance lurbinectedin plus atezolizumab yielded a median OS of 13.2 months vs. 10.6 months for atezolizumab (HR 0.73, p=0.017) and PFS of 5.4 months vs. 2.1 months (HR 0.54, p<0.0001). CASPIAN reported a median OS of 12.9 months with durvalumab (vs. 10.5 months for EP; HR 0.75, p=0.0032) and PFS of 5.1 months (vs. 5.4 months; HR 0.80). Patients in both trials received induction with a chemotherapy immunotherapy combination. Grade 3/4 AEs were higher in IMforte's combination (38% vs. 22%), and the CASPIAN trial reported similar grade 3/4 AEs between treatment arms. IMforte trial showed more myelosuppression (e.g., anemia 8%, neutropenia 7%) and CASPIAN more immune-related AEs (20% vs. 3%). Cost analysis revealed IMforte's ICER at $1,071,238/QALY versus CASPIAN durvalumab at $165,182/QALY, both exceeding the $150,000/QALY threshold but with durvalumab closer to cost-effectiveness. Our institutional drug acquisition cost was calculated to be $319,735 for atezolizumab plus lurbectinidin (12 months) vs $111,312 for duvalumab(12 months) maintenance, approximately. Conclusions: The IMforte combination offers superior PFS and potentially longer OS than CASPIAN's durvalimab-based regimen, but with increased bone marrow toxicity and significantly higher costs. CASPIAN's regimen is more cost-effective, making it a viable option in resource-constrained settings, and lurbenectin can be used as a following line of treatment after progression on durvalumab. The IMforte trial did not allow a crossover; hence, it is unknown if early introduction of lurbecnectin for ES-SCLC will better survival rather than when used as a subsequent line treatment. These findings inform treatment selection for ES-SCLC, balancing efficacy, safety, and economic considerations.