Nivolumab Yields High Clinical CR Rates Allowing for Surgery Omission in dMMR/MSI-H Endometrial Cancer

Nivolumab in dMMR/MSI-H

Endometrial Cancer | Image Credit:

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Treatment with nivolumab (Opdivo) led to clinical complete responses (CRs) in 80% of patients with resectable mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) endometrial cancer and many patients were able to omit surgery, according to findings from the phase 2 NIVEC trial (NCT05795244) presented at the 2025 SGO Annual Meeting on Women’s Cancer.1 Additionally, no patients in the study experienced disease recurrence at any point during the follow-up period, and the trial has entered the stage 2 portion where it is currently recruiting patients.

Patients treated with nivolumab (n = 15), achieved a clinical CR rate of 80.0% with no evidence of tumor on imaging and biopsy. Among the 12 patients with a clinical CR, 7 did not undergo surgery after receiving the immunotherapy and are in follow-up. The 3 patients who did not experience a CR had a partial response as their pathological best response; 2 of these patients had stage IA disease and 1 had stage IB.

In a presentation of the data, Yong Jae Lee, MD, PhD, of the Department of Obstetrics and Gynecology at Yonsei University College of Medicine in Korea, detailed 2 cases where patients had a great response to treatment. “One patient had a stage IIIC endometrioid type, grade 2 cancer with MLH1 and PMS2 loss. The patient had a 3.6 cm endometrial tumor with [aortocaval] lymph node metastasis. After 6 cycles of nivolumab, the tumor was completely resolved in imaging and the biopsy. Another patient had a stage IIIC endometrioid type, grade 3 cancer with MLH1 and PMS2 loss. The patient had a 12 cm endometrial tumor, more than 50% myometrial invasion, and cervical stromal invasion, with pelvic and paraaortic lymph node metastasis. After 6 cycles of nivolumab, the tumor was also completely resolved.”

Furthermore, the safety profile of nivolumab was also promising as no adverse effects (AEs) led to treatment discontinuation. Two grade 3/4 AEs occurred which included skin rash/dermatitis (3%) and anemia (3%). The most common any-grade toxicities were skin rash/dermatitis (30%), hypothyroidism/thyroiditis (15%), increased aspartate aminotransferase/alanine aminotransferase levels (15%), and increased thyroid-stimulating hormone levels (6%).

Putting the Study Under the Microscope

“The standard treatment for resectable endometrial cancer primarily involves surgery often combined with chemotherapy and/or radiation. However, up to 38% of patients experience recurrence and the risk of complications and treatment-related toxicities remain a significant concern,” Lee said in the presentation. “Current treatment strategies [are] particularly challenging [for] patients with severe comorbidities or those requiring fertility preservation. Immune checkpoint blockade has demonstrated efficacy and safety in advanced and recurrent dMMR endometrial cancer [and] neoadjuvant chemotherapy with immune checkpoint blockade has demonstrated promising outcomes in various dMMR tumors. This trial investigates the potential of PD-1 blockade in resectable dMMR endometrial cancer.”

NIVEC is a multicenter, prospective trial enrolling patients with stage I to III surgically resectable dMMR or MSI-H endometrial cancer, including those with carcinosarcoma, across 7 institutions in Korea.1,2 Patients enrolled have an ECOG performance score of 0 or 1 and cannot have received prior immune checkpoint inhibitor therapy.1 The primary end point of the study is pathologic or clinical CR rate and secondary end points include objective response rate, progression-free survival, overall survival, and safety.

The second stage of the study is enrolling an additional 15 patients for a total of 30 patients in the study as efficacy was demonstrated in stage 1 with more than 4 responses observed. In part 2, efficacy will be demonstrated when more than 13 patients achieve a CR. The study is using a Simon’s 2-stage minimax design.

Nivolumab is administered intravenously at 480 mg every 4 weeks for 6 cycles followed by imaging and biopsy. Those with residual disease proceed to surgery and adjuvant therapy, whereas those with a clinical CR undergo follow-up every 3 months and do not require surgery.

Patients in part 1 of the study were a median age of 57 years (range, 27-75) with clinical stage I (73.3%) and III (26.7%) disease. Most patients had endometrioid histology (93.3%), but 1 patient (6.7%) had mixed histology of endometrioid and clear cell. Histologic grades included well-differentiated (53.3%), moderate-differentiated (20.0%), and poor-differentiated (26.7%).

Disclosures: Lee cited having personal financial interests with AstraZeneca, MSD, and Takeda, as well as having institutional financial interests with Corcept Therapeutics and ONO.

References

1. Lee YJ, Lee YY, Park JY, et al. A phase II study of induction PD-1 blockade (nivolumab) in patients with surgically completely resectable mismatch repair deficient endometrial cancer (NIVEC). Presented at: 2025 SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Abstract 852136.
2. Study of induction PD-1 blockade (nivolumab) in patients with surgically complete resectable mismatch repair deficient endometrial cancer (NIVEC). ClinicalTrials.gov. Updated January 23, 2024. Accessed March 15, 2025. https://clinicaltrials.gov/study/NCT05795244