Clinical Summary: 

• Brian Slomovitz, MD, discusses results from the phase 3 KEYNOTE-C93 trial comparing first-line pembrolizumab monotherapy with carboplatin plus paclitaxel in patients with advanced or recurrent mismatch repair–deficient endometrial cancer.

• Pembrolizumab significantly improved progression-free survival compared with chemotherapy (38.2 vs 8.4 months; HR, 0.57), with fewer grade ≥3 treatment-related adverse events and clinically meaningful improvements in patient-reported quality of life.

• These findings support pembrolizumab monotherapy as a chemotherapy-free first-line option for patients with advanced or recurrent mismatch repair–deficient endometrial cancer, although overall survival benefit remains unconfirmed and the regimen was not directly compared with chemotherapy plus immunotherapy.

Brian Slomovitz, MD, Mount Sinai Medical Center, Miami Beach, Florida, discusses results from the phase 3 KEYNOTE-C93 trial comparing first-line pembrolizumab monotherapy with carboplatin plus paclitaxel in patients with advanced or recurrent mismatch repair–deficient (dMMR) endometrial cancer. 

Dr Slomovitz reviews the significant and durable progression-free survival benefit observed with pembrolizumab monotherapy, along with reduced high-grade treatment-related toxicity and clinically meaningful improvements in quality of life compared with chemotherapy. He also discusses the potential role of single-agent pembrolizumab as a chemotherapy-free treatment option and the importance of balancing efficacy, tolerability, and patient preferences when selecting first-line therapy.

Transcript: 

Hi, I'm Dr Brian Slomovitz. I'm the director of gynecologic oncology at Mount Sinai Medical Center in Miami Beach, Florida.

At the ESMO meeting this year, I had the great opportunity to present our work, C93, which is a first-line study in endometrial cancer comparing single-agent pembrolizumab, a chemo-free option, versus carboplatin/paclitaxel in patients with advanced or recurrent mismatch repair-deficient (dMMR) endometrial cancer.

We know that there is a tremendous interest from patients to have chemotherapy-free options. We also know that the dMMR patient population is really one of the most immunogenic tumors that we treat.

We've shown in the past in second-line trials that immunotherapy by itself, pembrolizumab in pre-treated patients, had a 48% response rate and a median duration of response that wasn't reached. We also know that recently, the first-line standard of care for patients with endometrial cancer has been chemotherapy plus immunotherapy.

In this trial, we sought to evaluate single-agent pembrolizumab versus chemotherapy. We enrolled 299 patients. Patients on the immunotherapy arm received it for 18 cycles, or about 2 years. Patients on the chemotherapy arm received it for 6 cycles every 3 weeks.

What we found is that progression-free survival was statistically significantly improved with pembrolizumab, with a hazard ratio of 0.57, representing a 43% decreased risk of progression or death in those patients with these tumors.

In addition, the median progression-free survival by months was 38 versus 8, again demonstrating a fourfold improvement in median progression-free survival.

When we looked at the toxicity profiles, we found that there were about 3 times higher grade ≥3 toxicities in the chemotherapy arm. There was also the percentage of patients that had a decrease due to discontinuation was lower in the pembrolizumab arm.

I think very importantly, I don't want to say most, but almost equally as important to the efficacy data is that we saw an improvement in quality of life in those patients who took pembrolizumab versus chemotherapy.

We looked at overall survival, and it was 0.77, not statistically significant, but there was a high crossover rate. Eighty-five percent of those patients on chemotherapy who progressed crossed over and had an immune checkpoint inhibitor.

What's the summary? Single-agent pembrolizumab has a statistically significant improvement in progression-free survival in patients with dMMR advanced or recurrent endometrial cancer.

There was lower grade ≥3 toxicity in those patients treated with pembrolizumab than those patients treated with chemotherapy.

Finally, there was an improved quality of life, which we feel now, especially for those patients who want to prioritize a chemotherapy-free regimen, we feel that this is definitely one of the strong options for those patients in the treatment of their disease.

We're really excited not only about this data, there's other data at this meeting being presented in endometrial cancer, but truthfully, as a gynecologic oncologist, I'm really thrilled that we are focusing more and more on these diseases to come up with better treatment options because there are really a lot of patients that need better treatment options.

Source: 

Slomovitz B, et al. KEYNOTE-C93/GOG-3064/ENGOT-en15: Phase 3, randomized, open-label study of first-line (1L) pembrolizumab (pembro) vs carboplatin (C) + paclitaxel (P) in mismatch repair-deficient (dMMR) advanced or recurrent endometrial carcinoma (a/rEC). Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA12.