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Background and Importance Several drugs targeting the programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1), in combination with platinum-based chemotherapy (ChT), are under evaluation for the treatment of recurrent or advanced endometrial cancer (EC) with deficient mismatch repair (dMMR). However, there are no head-to-head trials comparing these regimens, which limits their therapeutic positioning.Aim and Objectives To evaluate whether pembrolizumab, dostarlimab, durvalumab, durvalumab plus olaparib, and atezolizumab –each in combination with chemotherapy– can be considered equivalent therapeutic alternatives (ETAs) for patients with advanced or recurrent dMMR EC, through an adjusted indirect treatment comparison (ITC).Material and Methods A systematic bibliographic search for clinical trials (CTs) was conducted in PubMed. Inclusion criteria: phase II/III, randomised trials with comparable populations, follow-up durations, common comparator and definition of recurrent or advanced EC. Efficacy outcomes used for comparison: Hazard ratio (HR) for progression-free survival (PFS) and for overall survival (OS). Indirect treatment comparison (ITC) was conducted using Bucher method, employing dostarlimab plus chemotherapy as the reference treatment, selected for showing the best numerical HR value vs standard chemotherapy, among those that add a single drug to chemotherapy. The delta value (∆, maximum acceptable difference used as a clinical criterion of equivalence) was derived according to the ETA guidelines 1 based on the threshold HR of 0.65 considered by the ESMO-MCBS (form 2b) as representing substantial clinical benefit. Accordingly, equivalence margin was set between 0.65 and its inverse, 1.54.Results Five clinical trials were identified. Results of the adjusted indirect comparison are shown in the table 1.Abstract 4CPS-301 Table 1 Treatment PFS H.R (95% CI) OS H.R (95% CI) Dostarlimab+ChT Reference Reference Pembrolizumab+ChT 0,8 (0,381-1,678) 0,526 (0,172-1,608) Atezolizumab+ChT 0,778 (0,379-1,597) 0,73 (0,255-2,1) Durvalumab 0,667 (0,284-1,565) 0,882 (0,255-3,054) Durvalumab+ChT+Olaparib 0,683 (0,293-1,593) 1,071 (0,297-3,865) Conclusion and Relevance ITC showed no statistically or clinically significant differences among the five therapies. Nevertheless, pembrolizumab showed clinically relevant difference compared to the reference treatment, but no statistically significant improvement in OS in the clinical trial. Furthermore, durvalumab plus olaparib, which add two drugs to chemotherapy was consequently associated with higher toxicity.References and/or Acknowledgements 1. Alegre-Del Rey EJ, Fénix-Caballero S, Castaño-Lara R, Sierra-García F. Assessment and positioning of drugs as equivalent therapeutic alternatives. Med Clin(Barc). 2014;143(2):85–90.Conflict of Interest No conflict of interest