Efficacy Outcomes Between Tarlatamab and Real-World Physicians’ Choice of Therapies for Previously Treated Extensive Stage Small Cell Lung Cancer

Abstract Background Tarlatamab, a bispecific T-cell engager immunotherapy, showed durable response with promising survival outcomes in patients with previously treated small cell lung cancer (SCLC) in the phase 2 DeLLphi-301 study. Given the lack of a comparator in DeLLphi-301, this analysis aimed to evaluate the relative efficacy of tarlatamab against physicians’ choice of therapies in real-world practice. Patients and Methods This analysis compared the outcomes of patients in DeLLphi-301 who received tarlatamab 10 mg (n = 97) with patients in real-world cancer clinics captured in the Flatiron Health database who received third or later-line comparator therapies for SCLC (n = 184). Propensity score weighting was used to adjust for differences in key prognostic factors between cohorts. Overall survival (OS), progression-free survival (PFS), time to treatment discontinuation (TTD), time to next treatment or death (TTNTD), and objective response rate (ORR) were compared after weighting. Results Tarlatamab was associated with significantly longer OS, PFS, TTD, and TTNTD, and higher ORR versus comparator therapies. After weighting, the hazard ratios (95% confidence interval [CI]) of tarlatamab versus comparator therapies were 0.45 (0.30, 0.68) for OS, 0.61 (0.43, 0.90) for PFS, 0.57 (0.39, 0.84) for TTD, and 0.45 (0.30, 0.66) for TTNTD. The odds ratio for ORR was 2.80 (95% CI: 1.44, 5.83). Conclusion The study findings suggest that tarlatamab offers potential clinical benefits relative to comparator treatments. This analysis underscores the potential of tarlatamab to become a new therapeutic option for previously treated SCLC, a disease that has historically been associated with extremely poor outcomes and limited treatment options.