Dr Eskander on the Potential Clinical Benefit of Nivolumab in dMMR Endometrial Cancer

“Can we start to really expand the patient population that we can consider for fertility-preserving medical management in the dMMR patient population beyond what we [used] previously in terms of hormonal strategies?”

Ramez N. Eskander, MD, an assistant professor in the Departments of Obstetrics, Gynecology, and Reproductive Sciences at the University of California (UC) San Diego School of Medicine; as well as the director for oncology of the clinical trials office at the UC San Diego Moores Cancer Center, discussed findings from the phase 2 NIVEC trial (NCT05795244) investigating the PD-1 inhibitor nivolumab (Opdivo) in patients with fully surgically resectable mismatch repair–deficient (dMMR) endometrial cancer.

At the 2025 SGO Annual Meeting on Women’s Cancer, Yong-Jae Lee, MD, PhD, of Yonsei University Hospital, presented findings from NIVEC, which explored a novel application of checkpoint inhibition beyond that studied in prior prospective randomized trials, Eskander began. Unlike historical studies that primarily assessed nivolumab in the advanced or metastatic endometrial cancer settings, NIVEC enrolled patients who would have been candidates for surgical tumor resection, he noted. The objective of the trial was to determine whether nivolumab could reduce tumor burden and elicit a meaningful clinical response preoperatively in this patient population.

Key study end points included pathologic complete response (pCR) rates, radiographic imaging assessments, and biopsy evaluations. Among the first 15 patients enrolled in stage 1 of the study, the pCR rate was 80%, indicating a substantial response to nivolumab in this cohort, Eskander said. This finding is significant, as patient eligibility for enrollment in the trial was not restricted to those traditionally considered for medical or hormonal endometrial cancer management, he explained.

The implications of these findings are notable for expanding the scope of fertility-preserving treatments available for patients with dMMR endometrial cancer, Eskander emphasized. Historically, the management of this disease primarily relied on hormonal therapy; however, this study suggests that immune checkpoint blockade may be a viable alternative in select patients, he stated. The high pCR rate with nivolumab in NIVEC raises the possibility of incorporating immunotherapy into treatment paradigms aimed at preserving fertility, broadening the options available for younger patients or those seeking nonsurgical interventions, according to Eskander. Further research is warranted to validate these findings and refine patient selection criteria for this approach, he concluded.