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

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

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

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.

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.

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.

In this paper, Immunotherapy added to chemotherapy improves disease-free and overall survival in advanced and metastatic endometrial cancer, and while endometrial cancer is the malignancy with the highest prevalence of MMRd/MSI-H it is an agnostic prognostic biomarker, and adding immunotherapy to the MMRp/MSS population may have an effect on outcomes.


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