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Background and Importance For recurrent or advanced endometrial cancer (EC) with proficient mismatch repair (pMMR), several immune checkpoint inhibitors targeting PD-1 or PD-L1 are being investigated in combination with platinum-based chemotherapy (ChT). The absence of direct comparative studies limits informed decision-making regarding their relative clinical benefit.Aim and Objectives To explore the comparative efficacy of immunotherapy-based combinations with chemotherapy –specifically those including pembrolizumab, dostarlimab, durvalumab, durvalumab plus olaparib, and atezolizumab–, in the treatment of pMMR EC, through an adjusted indirect treatment comparison (ITC) for assessing their potential equivalence as equivalent therapeutic alternatives (ETAs).Material and Methods A structured search strategy was applied in PubMed to identify phase II/III randomised clinical trials assessing immune checkpoint inhibitors in combination with chemotherapy for the treatment of advanced or recurrent EC with pMMR. Eligible studies requirements: comparable populations, consistent definitions of disease stage, common comparator and similar follow-up durations. Overall survival (OS) and progression-free survival (PFS), both expressed as hazard ratio (HR), were selected as the outcomes for efficacy comparison. ITC was conducted using Bucher method, using dostarlimab plus chemotherapy as the reference treatment for showing the best numerical HR value vs standard chemotherapy, among those that add a single drug to chemotherapy. Clinical equivalence margin (∆) was established between 0.65 and its reciprocal, 1.54, in accordance with the ETA guideline 1 and the ESMO-MCBS (form 2b), which considers a HR of 0.65 indicative of substantial clinical benefit.Results Five clinical trials met the eligibility criteria. Findings from the adjusted indirect comparison are summarised in the table 1.Abstract 4CPS-316 Table 1 Treatment PFS HR (95% CI ) OS HR (95% CI ) Dostarlimab+ChT Reference Reference Pembrolizumab+ChT 1,027 (0,741-1,423) 0,912 (0,578-1,441) Atezolizumab+ChT 0,826 (0,587-1,162) 0,73 (0,463-1,151) Durvalumab+ChT 0,987 (0,698-1,397) 0,802 (0,49-1,313) Durvalumab+ ChT+Olaparib 1,101 (0,7-1,733) 1,058 (0,636-1,761) Conclusion and Relevance No clinically or statistically meaningful differences were observed between the evaluated PD-1/PD-L1 inhibitor combinations in patients with pMMR advanced or recurrent endometrial cancer. Among them, the regimen combining durvalumab and olaparib showed a higher toxicity over the others options which only add one drug to chemotherapy, suggesting limited added clinical value.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