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Adding the PD-1 antibody dostarlimab to first-line chemotherapy for advanced endometrial cancer cut progression by 72% in tumours with defective mismatch repair and by about a third overall, and later improved survival.
Double-blind, placebo-controlled phase 3 trial of 494 patients with primary advanced (stage III-IV) or first recurrent endometrial cancer randomised to dostarlimab or placebo with carboplatin-paclitaxel for six cycles, then dostarlimab or placebo maintenance for up to three years. Primary endpoints were PFS in the dMMR/MSI-high population and in the overall population, and OS.
In dMMR tumours (about 24% of patients), 24-month PFS was 61.4% vs 15.7% (HR 0.28); overall, 36.1% vs 18.1% (HR 0.64). Overall survival was improved in the whole population (HR 0.69 in the 2024 analysis). Together with NRG-GY018 (pembrolizumab), it made chemo-immunotherapy the first-line standard for advanced endometrial cancer and mismatch repair testing routine.
Women with newly diagnosed advanced or recurrent endometrial cancer should receive a PD-1 antibody (dostarlimab or pembrolizumab) with their chemotherapy, and mismatch repair testing is now essential because women with dMMR tumours gain a very large and durable benefit. The gain in mismatch-repair-proficient tumours is real but smaller, and molecular classification (POLE, p53, MMR) is increasingly used to decide who benefits most.
Shares Mansoor Raza Mirza, Uterine carcinosarcoma, Mismatch-repair-deficient endometrial cancer, Advanced or recurrent endometrial cancer.
Shares Mismatch-repair-deficient endometrial cancer, Advanced or recurrent endometrial cancer, Dostarlimab, GSK.
Shares Mismatch-repair-deficient endometrial cancer, Advanced or recurrent endometrial cancer, Dostarlimab, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Mismatch-repair-deficient endometrial cancer, Advanced or recurrent endometrial cancer, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Endometrial cancer.
Shares Mismatch-repair-deficient endometrial cancer, Advanced or recurrent endometrial cancer, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Endometrial cancer.
Shares Lines of therapy, Progression-free survival (PFS), Overall survival (OS), No one can predict who responds to immunotherapy.
Shares Lines of therapy, Progression-free survival (PFS), Overall survival (OS), No one can predict who responds to immunotherapy.
Shares Mismatch-repair-deficient endometrial cancer, Dostarlimab, GSK, Endometrial cancer.