The New England Journal of MedicineDostarlimab for Primary Advanced or Recurrent Endometrial Cancer

Enhanced Efficacy of Dostarlimab in Advanced Endometrial Cancer Linked to Genetic Biomarkers

This article presents findings from a phase 3 clinical trial evaluating the effectiveness of dostarlimab, an immune-checkpoint inhibitor, in combination with chemotherapy for the treatment of primary advanced or recurrent endometrial cancer. It emphasizes the significant benefits observed particularly in patients with specific genetic profiles, providing critical insights into personalized cancer treatment strategies.

Key Points:

• Dostarlimab targets the programmed cell death 1 receptor and is studied for its potential in treating endometrial cancer when combined with chemotherapy.
• The study was a phase 3, global, double-blind, randomized, placebo-controlled trial involving patients with advanced stage III or IV, or first recurrent endometrial cancer.
• Participants were randomly assigned to receive either dostarlimab (500 mg) plus carboplatin and paclitaxel, or a placebo alongside the same chemotherapy regimen.
• Treatment cycles consisted of six three-weekly sessions followed by maintenance doses of dostarlimab (1000 mg) or placebo every six weeks for up to three years.
• In patients with mismatch repair–deficient (dMMR) and microsatellite instability–high (MSI-H) tumors, dostarlimab significantly outperformed the placebo in terms of progression-free survival at 24 months (61.4% vs. 15.7%).
• The hazard ratio for progression or death in the dMMR–MSI-H population was 0.28, indicating a markedly lower risk when treated with dostarlimab.
• Overall, the dostarlimab group showed improved progression-free survival across all participants at 24 months (36.1% vs. 18.1% in the placebo group).
• Overall survival at 24 months also favored dostarlimab (71.3% vs. 56.0% for placebo), with a hazard ratio for death at 0.64.
• Common adverse events included nausea, alopecia, and fatigue, with severe and serious adverse events more frequent in the dostarlimab group.

Mismatch repair-deficient tumors (MMRd) occur in up to 30% of all endometrial cancers (EC).

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