Introduction/Background Immunotherapy represents a paradigm shift in endometrial cancer treatments, especially in those with mismatch repair deficient profiles (MMRd/MSI-H). Accumulating evidence supported the adoption of immunotherapy in combination with chemotherapy in a first line setting. Recently, the results of the ongoing RUBY (part 1), NRG-GY018, AtTEnd, and DUO-E trials were released. Here, we aim to reported pooled data of those four studies.

Methodology This is a meta-analysis of phase III trials (RUBY (part 1), NRG-GY018, AtTEnd, and DUO-E) evaluating the role of immunotherapy in first-line setting for advanced/recurrent endometrial cancer

Results The pooled data of 2,320 patients included in those trials supported the adoption of chemotherapy plus immunotherapy, being related to significant improvement in progression-free survival in comparison to chemotherapy alone (HR: 0.70 (95%CI: 0.62, 0.79)) in all comers. The progression-free survival is more pronounced in the MMRd/MSI-H tumor (n=563; HR: 0.33 (95%CI: 0.23, 0.43)). This benefit, even less robust, is present also in the MMRp/MSS group (n=1,757; HR: 0.74 (95%CI: 0.60, 0.91)). Pooled data showed that chemotherapy plus immunotherapy improves overall survival in comparison to chemotherapy alone, in all comers (HR: 0.75 (95%CI: 0.63, 0.89)). However, the maturity rates of survival data are low.

Conclusion Exploratory analyses are ongoing to identify non-responding patients who deserve to be included in clinical trials and responding patients who deserve to be treated with chemotherapy-free regimens. In this latter setting, de-escalation would be proposed to improve quality of life, without neglecting long-term oncologic outcomes.

Disclosures None.