Adding immunotherapy to first-line treatment of advanced and metastatic endometrial cancer

Background Immunotherapy has transformed the endometrial cancer treatment landscape , particularly for those exhibiting mismatch repair deficiency (MMRd/MSI-H). A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed. Materials and Methods This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer. Results The pooled data from 2,320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone (Hazard Ratio (HR): 0.70, 95% Confidence Interval (CI): 0.62, 0.79) across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n=563; HR: 0.33, 95% CI: 0.23, 0.43). This benefit, albeit less robust, persists in the MMRp/MSS group (n=1,757; HR: 0.74, 95% CI: 0.60, 0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR: 0.75, 95% CI: 0.63, 0.89). However, overall survival data maturity remain low. Conclusions The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.