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Background and Importance Despite recent advances, first-line chemoimmunotherapy with PD-L1 inhibitors for extensive-stage small-cell lung cancer (ES-SCLC) provides only modest survival benefits. Tislelizumab has been recently approved by the European Commission, but head-to-head comparisons among available immunotherapies are lacking, highlighting the need for indirect analyses to guide optimal treatment selection.Aim and Objectives To determine whether tislelizumab, atezolizumab and durvalumab can be considered clinically equivalent therapeutic alternatives (CETAs) in patients with ES-SCLC through an adjusted indirect treatment comparison (ITC) using a common comparator.Material and Methods A literature search was conducted to identify phase III clinical trials (CTs) involving tislelizumab, atezolizumab or durvalumab in comparable populations, study durations, and endpoints. The primary outcomes were progression-free survival (PFS) and overall survival (OS). An ITC between tislelizumab, atezolizumab and durvalumab was performed using the Bucher method, supported by the Canadian Agency for Drugs and Technologies in Health (CADTH) ITC calculator. According to ESMO, a hazard ratio (HR) <0.65 (and its inverse, 1.54) is considered clinically meaningful for treatment differences in this setting. Results were graphically analysed, focusing on the relative position of the 95% CI relative to the predefined equivalence margin.Results Three CTs were included: RATIONALE-312 (tislelizumab), IMpower133 (atezolizumab) and CASPIAN (durvalumab). The selected trials were phase III, multicentre, randomised, placebo-controlled studies involving patients with ES-SCLC in first-line treatment and Performance Status 0-1. The individual CTs outcomes in terms of PFS were tislelizumab HR=0.64 (95% CI 0.52-0.78), atezolizumab HR=0.77 (95% CI 0.63-0.96) and durvalumab HR=0.78 (95% CI 0.65-0.94); and in terms of OS 0.75 (95% CI 0.61-0.93), 0.70 (95% CI 0.54-0.91) and 0.73 (95% CI 0.59-0.91) respectively. The results of the ITC are summarised in table 1. Abstract 2SPD-021 Table 1ITC PFS HR (95% CI) OS HR (95% CI) Tislelizumab vs atezolizumab 0.83 (0.62-1.11) 1.07 (0.77-1.50) Tislelizumab vs durvalumab 0.82 (0.62-1.08) 1.03 (0.83-1.28) Atezolizumab vs durvalumab 0.99 (0.73-1.33) 0.96 (0.68-1.35) No statistically significant difference was observed for PFS or OS.Conclusion and Relevance Tislelizumab, atezolizumab, and durvalumab show no significant differences in PFS or OS. Given similar mechanisms and consistent placebo outcomes, they may be considered CETAs for ES-SCLC first-line treatment, despite potential OS bias from subsequent therapies, particularly in the RATIONALE-312, where a higher proportion of patients received subsequent systemic therapies—including immunotherapy.Conflict of Interest No conflict of interest