During the 2026 Congress of the European Society for Medical Oncology (ESMO), Oncology Frontier conducted an on-site interview in Barcelona, Spain, with Professor Brian M. Slomovitz, Global Principal Investigator of the KEYNOTE-C93 study and Director of Gynecologic Oncology at Mount Sinai Medical Center, United States.KEYNOTE-C93 (NCT05173987) was presented as LBA12 during a Presidential Symposium, delivering a major finding: this Phase III study demonstrated for the first time that first-line pembrolizumab monotherapy significantly improved progression-free survival (PFS) compared with standard carboplatin plus paclitaxel chemotherapy in patients with mismatch repair-deficient (dMMR) advanced or recurrent endometrial cancer. The findings offer the first “chemotherapy-free” immunotherapy option for this patient population, which has historically relied on chemotherapy.
This article is based on the on-site interview recording and presents Professor Slomovitz’s key perspectives on the study findings, subsequent treatment sequencing, potential implications for clinical guidelines, and major research developments at the congress in a Q&A format.
Could you introduce the KEYNOTE-C93 study? What is the current established treatment landscape for patients with dMMR advanced or recurrent endometrial cancer? What are the key PFS and OS findings from this study?
Professor Brian M. Slomovitz: In KEYNOTE-C93, we evaluated pembrolizumab monotherapy versus carboplatin plus paclitaxel in patients with advanced or recurrent dMMR endometrial cancer.
The rationale for this study stems from KEYNOTE-158, which evaluated pembrolizumab monotherapy in previously treated patients with advanced MSI-H/dMMR endometrial cancer. In that previously treated population, the objective response rate (ORR) was 48%, and median duration of response (DoR) had not been reached.
Over the past several years, however, chemotherapy combined with immunotherapy has become the standard treatment for advanced or recurrent endometrial cancer, particularly in the dMMR population, where hazard ratios (HRs) have been approximately 0.3–0.4.
KEYNOTE-C93 enrolled a total of 299 patients and was designed to evaluate pembrolizumab monotherapy against standard chemotherapy.
There is one important point to clarify regarding OS. A substantial proportion of patients received crossover checkpoint inhibitor therapy during or after the trial, which to some extent diluted the OS difference in the intention-to-treat (ITT) population. We subsequently conducted sensitivity analyses to adjust for this crossover effect. The results continued to suggest a trend toward an OS benefit with pembrolizumab. In other words, crossover treatment likely obscured the true OS benefit in the ITT population.
From a clinical practice perspective, we have found that a chemotherapy-free regimen is now a feasible option and is preferred by many patients, particularly given the lower incidence of grade ≥3 toxicities and improvements in quality of life. These advantages were also demonstrated in this study.
After immunotherapy has been used in the first-line setting, what role does immunotherapy have in subsequent treatment lines for patients with dMMR endometrial cancer? Under what circumstances would you still combine immunotherapy with other treatments? How can this treatment sequencing benefit patients?
Professor Brian M. Slomovitz: We believe KEYNOTE-C93 has established pembrolizumab monotherapy as a potentially viable first-line option for dMMR tumors. The next question is: what should we do for patients who develop resistance or experience recurrence after pembrolizumab monotherapy?
Chemotherapy remains a clear treatment option. Although we have not traditionally been accustomed to using carboplatin plus paclitaxel in the second-line setting, now that a chemotherapy-free immunotherapy regimen is available in the first line, reserving chemotherapy for second-line treatment is certainly a strategy we will consider in the future.
Another area of considerable interest is antibody-drug conjugates (ADCs). At this year’s ESMO Congress, the TroFuse-005 study will be presented, evaluating sacituzumab tirumotecan (sac-TMT), a TROP2-targeted ADC, as second-line treatment for advanced or recurrent endometrial cancer. This agent has demonstrated very promising antitumor activity.
Endometrial cancer itself is a highly heterogeneous disease. Some patients may benefit from therapies targeting hormone-related pathways, while others may respond to treatments directed at different cellular and molecular pathways. Therefore, we have a broad therapeutic arsenal available. Introducing a chemotherapy-free first-line option helps address an unmet need in subsequent treatment lines: it allows chemotherapy to remain available as an option for patients later in their treatment journey.
What immediate impact do you expect the KEYNOTE-C93 findings to have on clinical practice guidelines? When might pembrolizumab be incorporated into treatment recommendations?
Professor Brian M. Slomovitz: Pembrolizumab has been used in cancer treatment for several years. Based on the KEYNOTE-C93 findings, we believe it can have an immediate impact on the standard of care, changing how we offer treatment options to patients with advanced or recurrent dMMR tumors.
More specifically, after discussion between the medical team and the patient, if the patient genuinely prefers a chemotherapy-free regimen—one with established efficacy, lower toxicity, and the potential to improve quality of life—it can be implemented in clinical practice almost immediately.
There is no need to wait for lengthy guideline updates. The drug is already widely used in clinical practice; what we are updating is the treatment sequencing and positioning in the first-line setting.
Which study presented at this year’s congress impressed you the most, and why?
Professor Brian M. Slomovitz: The 2026 ESMO Congress was an exciting meeting for gynecologic oncology. Personally, I was most looking forward to the evaluation of antibody-drug conjugates in recurrent disease, particularly sacituzumab tirumotecan (sac-TMT) in patients with endometrial cancer who experience recurrence after first-line treatment. Those are the data I found most exciting.
Beyond gynecologic oncology, I was also very encouraged by the mRNA vaccine data. This is an extremely promising field, and we hope these approaches will not only become established in a single tumor type but will also be applicable across multiple cancer types.
