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A chemo-free first-line option may be on the horizon for some endometrial cancer patients. The phase 3 KEYNOTE-C93 trial found that pembrolizumab monotherapy nearly halved the risk of disease progression compared to standard carboplatin-paclitaxel chemotherapy in patients with mismatch repair–deficient (dMMR) advanced or recurrent endometrial cancer. The safety profile also strongly favored pembrolizumab, with far fewer severe side effects.
A chemo-free first-line option may be on the horizon for some endometrial cancer patients. The phase 3 KEYNOTE-C93 trial, presented at the 2026 ESMO Congress and published in The Lancet, showed that pembrolizumab (Keytruda) monotherapy significantly improved progression-free survival (PFS) compared to carboplatin plus paclitaxel in patients with dMMR advanced or recurrent endometrial cancer — a subgroup that makes up roughly 25–30% of this patient population.
The median PFS was 38.2 months with pembrolizumab versus just 8.4 months with chemotherapy. While overall survival (OS) numerically favored pembrolizumab, it didn't reach statistical significance — likely influenced by the fact that 85% of patients in the chemo arm crossed over to immunotherapy after progression. Quality of life scores also improved with pembrolizumab and declined with chemotherapy at week 12.
By the Numbers:
Why it matters: This trial offers a compelling case for a chemotherapy-free first-line strategy in dMMR endometrial cancer — a highly immunogenic subgroup. With a dramatically better safety profile and durable responses, pembrolizumab monotherapy could meaningfully expand treatment choices for patients who want to avoid chemotherapy's harsh side effects.
