Preliminary results from the phase 2 NIVEC trial presented at the 2025 Society of Gynecologic Oncology (SGO) Annual Meeting on Women's Cancer show that nivolumab (Opdivo) achieved an impressive 80% clinical complete response (CR) rate in patients with resectable mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) endometrial cancer, potentially eliminating the need for surgery in many patients.
The multicenter, prospective trial enrolled 15 patients with stage I to III surgically resectable dMMR or MSI-H endometrial cancer across seven institutions in Korea. After receiving nivolumab, 12 patients achieved a clinical CR with no evidence of tumor on imaging and biopsy. Among these responders, seven patients were able to avoid surgery entirely and remain in follow-up. Notably, no patients experienced disease recurrence during the follow-up period.
"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," explained Dr. Yong Jae Lee of Yonsei University College of Medicine in Korea, who presented the findings.
Impressive Responses in Advanced Disease
Dr. Lee highlighted two particularly remarkable cases during his presentation. One patient with stage IIIC endometrioid type, grade 2 cancer with MLH1 and PMS2 loss had a 3.6 cm endometrial tumor with aortocaval lymph node metastasis. After six cycles of nivolumab, imaging and biopsy showed complete resolution of the tumor.
In another case, a patient with stage IIIC endometrioid type, grade 3 cancer with MLH1 and PMS2 loss presented with a 12 cm endometrial tumor, more than 50% myometrial invasion, cervical stromal invasion, and pelvic and paraaortic lymph node metastasis. This patient also experienced complete tumor resolution after six cycles of nivolumab.
The three patients who did not achieve a complete response still demonstrated partial responses. Two of these patients had stage IA disease, and one had stage IB disease.
Study Design and Patient Characteristics
The NIVEC trial uses a Simon's 2-stage minimax design. Patients received nivolumab intravenously at 480 mg every four weeks for six cycles, followed by imaging and biopsy. Those with residual disease proceeded to surgery and adjuvant therapy, while those with a clinical CR underwent follow-up every three months without surgery.
Patients in the first part of the study had a median age of 57 years (range, 27-75) with predominantly clinical stage I (73.3%) and stage III (26.7%) disease. Most patients (93.3%) had endometrioid histology, with one patient (6.7%) having mixed endometrioid and clear cell histology. Histologic grades included well-differentiated (53.3%), moderate-differentiated (20.0%), and poor-differentiated (26.7%).
All participants had an ECOG performance score of 0 or 1 and had not received prior immune checkpoint inhibitor therapy. The primary endpoint of the study is pathologic or clinical CR rate, with secondary endpoints including objective response rate, progression-free survival, overall survival, and safety.
Favorable Safety Profile
The safety profile of nivolumab was promising, with no adverse effects leading to treatment discontinuation. Only two grade 3/4 adverse events occurred: one case of skin rash/dermatitis (3%) and one case of 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%).
Implications for Treatment Paradigm
Current treatment strategies for endometrial cancer present particular challenges for patients with severe comorbidities or those requiring fertility preservation. The NIVEC trial results suggest that PD-1 blockade with nivolumab could offer a less invasive alternative for patients with dMMR or MSI-H endometrial cancer.
"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," Dr. Lee noted. "This trial investigates the potential of PD-1 blockade in resectable dMMR endometrial cancer."
Moving Forward
Based on the positive results from the first stage of the trial, with more than four responses observed, the study has now entered its second stage. Researchers are enrolling an additional 15 patients for a total of 30 participants. In part 2, efficacy will be demonstrated when more than 13 patients achieve a CR.
The findings from the NIVEC trial represent a potentially significant advancement in the treatment of dMMR/MSI-H endometrial cancer, offering the possibility of avoiding surgery and its associated complications while maintaining excellent disease control.
