November 4th, 2026
Summary by Catlin Nalley
Pembrolizumab monotherapy significantly improved progression-free survival (PFS) compared with carboplatin-paclitaxel chemotherapy in patients with mismatch repair-deficient (dMMR) advanced or recurrent endometrial carcinoma, according to phase III KEYNOTE-C93/GOG-3064/ENGOT-en15 findings presented at the 2026 European Society for Medical Oncology (ESMO) Congress (Abstract LBA12) and published simultaneously in The Lancet.
After a median follow-up of approximately 3 years, patients receiving pembrolizumab had a median PFS of 38.2 months, compared with 8.4 months for those receiving chemotherapy. The findings suggest that immunotherapy alone could provide a chemotherapy-free first-line option for selected patients whose tumors harbor this biomarker, particularly those seeking to avoid chemotherapy-associated toxicity.
“There's a strong desire among healthcare providers and patients and their families for a first-line, chemotherapy-free option for patients with advanced or recurrent endometrial cancer,” said study author Brian Slomovitz, MD, Director of Gynecologic Oncology and Deputy Director of the Braman Comprehensive Cancer Center at Mount Sinai Medical Center, during his ESMO presentation.
Approximately 30% of patients with advanced or recurrent endometrial cancer have dMMR tumors, a subtype characterized by defects in the cellular machinery responsible for correcting DNA replication errors. These tumors can accumulate mutations that make them particularly responsive to immune checkpoint inhibition.
“One unique opportunity is in mismatch repair–deficient, or dMMR, tumors, which are among the most immunogenic tumors that we treat,” he noted. “About 30% of patients with advanced or recurrent endometrial cancer have dMMR tumors.”
Although pembrolizumab is already used with platinum-based chemotherapy in first-line treatment, KEYNOTE-C93 investigated whether chemotherapy could be omitted altogether in this molecularly defined population.
Methods, Key Outcomes
KEYNOTE-C93 was a randomized, open-label phase III trial conducted at 122 sites across 24 countries. Investigators enrolled 299 patients with inoperable stage III or IV, advanced or recurrent endometrial carcinoma and centrally confirmed dMMR status. Participants had not received prior systemic treatment for advanced disease, although prior neoadjuvant or adjuvant systemic therapy was permitted if recurrence occurred at least 6 months after the last dose. Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 or 1.
Patients were randomized 1:1 to receive either pembrolizumab every 6 weeks for up to 18 cycles, approximately 2 years, or carboplatin plus paclitaxel every 3 weeks for six cycles. The chemotherapy group received no maintenance treatment, but crossover to pembrolizumab was permitted after confirmed disease progression.
The dual primary endpoints were PFS assessed by blinded independent central review and overall survival (OS). Overall response rate, duration of response, and patient-reported quality of life were also evaluated. The reported analysis, with an April 24, 2026, data cutoff, represented the final PFS analysis and an interim OS analysis.
Pembrolizumab reduced the risk of disease progression or death by 43% compared with chemotherapy, corresponding to a hazard ratio (HR) of 0.57 (95% CI: 0.42–0.79; P=0.0002). The prespecified statistical threshold for PFS was met.
Median PFS was 38.2 months with pembrolizumab versus 8.4 months with chemotherapy. At 36 months, an estimated 52.8% of patients receiving pembrolizumab remained progression-free, compared with 30.0% in the chemotherapy group.
Overall survival also numerically favored pembrolizumab, with an HR of 0.77 (95% CI: 0.52–1.15). Three-year OS rates were 70.7% with pembrolizumab and 62.0% with chemotherapy, but the difference was not statistically significant at this interim analysis, and OS follow-up remains ongoing.
Response Durability, Quality of Life & Safety
Objective response rates were similar between groups: 64.1% with pembrolizumab and 62.1% with chemotherapy. However, complete responses were more frequent with pembrolizumab (33.8% versus 26.2%), and responses appeared more durable. Median duration of response was not reached with pembrolizumab, compared with 10.2 months with chemotherapy. At 36 months, 70.7% of pembrolizumab responders remained in response, versus 40.0% of chemotherapy responders.
Patient-reported outcomes further favored immunotherapy. At week 12, pembrolizumab produced a 7.02-point between-group advantage in global health status and quality of life (95% CI, 2.54–11.50), a clinically meaningful difference. Physical, role, cognitive, and social functioning also favored pembrolizumab, while chemotherapy recipients reported greater symptom burdens, including fatigue, neuropathy, and muscle pain.
Grade 3 or higher treatment-related adverse events occurred in 18.1% of patients receiving pembrolizumab, compared with 50.7% undergoing chemotherapy. Anemia was the most common grade 3 or higher treatment-related adverse event reported in the chemotherapy arm, affecting 18.1%, versus 2.0% with pembrolizumab. Grade 3 or higher immune-mediated adverse events occurred in 7.4% of pembrolizumab recipients. Investigators reported no new safety signals.
"These results highlight the potential of a chemotherapy-free approach for certain patients with dMMR advanced or recurrent endometrial cancer, with pembrolizumab monotherapy demonstrating a clinically meaningful benefit in progression-free survival along with a favorable quality of life compared to chemotherapy," concluded Slomovitz. "After years of platinum-based chemotherapy serving as the frontline standard, these findings could help provide an additional treatment option beyond carboplatin plus paclitaxel in combination with pembrolizumab for these patients."