PD-1 blockade induces response in surgically resectable endometrial cancer
Key takeaways:
- Eighty percent of patients achieved clinical complete response to nivolumab.
- Researchers observed no recurrences during follow-up.
PD-1 blockade conferred benefit to certain women with surgically resectable endometrial cancer, findings presented at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer showed.
Nivolumab (Opdivo, Bristol Myers Squibb) induced “meaningful complete response” among those with mismatch repair-deficient disease, according to researchers.
Standard treatment for resectable endometrial cancer often consists of surgery, combined with chemotherapy and/or radiation. However, up to 22% of patients develop recurrence, and risk for treatment-related toxicity or complications remains a significant concern, Yong Jae Lee, MD, PhD, of Yonsei University College of Medicine in South Korea, said during a presentation.
Current treatment strategies are particularly challenging for women with severe comorbidities or those who require fertility preservation, Lee said.
Prior studies showed immune checkpoint blockade in the neoadjuvant setting conferred favorable outcomes for patients with certain mismatch repair-deficient tumors.
Lee and colleagues conducted the single-arm, phase 2 NIVEC study to assess the safety and efficacy of neoadjuvant nivolumab — an anti-PD-1 antibody — for women with resectable mismatch repair-deficient endometrial cancer.
In the study’s first stage, researchers enrolled 15 women (median age, 57 years; range, 27-75) with stage I to stage IIIC2 tumors determined by immunohistochemistry or microsatellite instability to be mismatch repair deficient. All women had ECOG performance status of 0 or 1, and 14 (93.3%) had endometrioid histology. No women had received prior immune checkpoint inhibitor therapy.
Patients received 480 mg IV nivolumab every 4 weeks for up to 6 months. Women who achieved clinical complete response after nivolumab therapy did not undergo surgery but continued with follow-up every 3 months. Those who had residual disease after neoadjuvant nivolumab proceeded to surgery and adjuvant therapy.
Pathologic or clinical complete response rate served as the primary endpoint. Secondary endpoints included objective response rate, PFS, OS and safety.
Twelve patients (80%) achieved clinical complete response to nivolumab, defined as no evidence of tumor on biopsy or imaging. Seven of those 12 patients did not undergo surgery. The five who did undergo surgery at their own request were found to have pathologic complete response, Lee said.
Researchers observed no recurrences during follow-up.
The most common adverse events included skin rash/dermatitis (30%), hypothyroidism/thyroiditis (15%) and increased aspartate aminotransferase or alanine aminotransferase (15%). Two patients experienced grade 3/grade 4 adverse events, with one case each of skin rash/dermatitis and anemia.
No treatment-related adverse events led to treatment discontinuation, Lee said.
The trial’s second stage will include an additional 15 women. Enrollment is continuing, Lee said.
Perspective
Back to TopI’d like to recognize the effort — and, frankly, the bravery — that it takes to move single-agent checkpoint inhibition into the neoadjuvant setting for patients who have had quite substantial disease burden.
The patients enrolled on this trial were older than one might anticipate if the intent is to explore this as a fertility-preserving strategy. In addition, the majority of patients had endometrioid histology and had stage I disease at the time of trial enrollment. Despite that, 80% had a clinical complete response.
In parallel, we saw three patients had absent expression of all MMR genes via immunohistochemistry. It’s intriguing — and provocative — to ask why they might lose expression of all of these simultaneously. In addition, if you look at the proportion of patients who had absent MLH1 and PMS2, it was approximately a third of the patients enrolled and treated. In contemporary trials, we see about 75% of our patients are mismatch repair deficient by epigenetic modulation, so we have to ask ourselves, what is the extrapolation of this information in a larger cohort? Further, what are the implications of this on generalizability to a larger patient population?
With respect to adverse events, there was a 15% rate of hypothyroidism, which is a “forever diagnosis” for most patients who develop this while receiving immune checkpoint inhibition.
We’re left to ask ourselves: In which patient population would we employ such a strategy, and what is our end goal? We understand there is a potential therapeutic strategy here and I commend the authors for sharing this information. I’m eager to see additional data with longer follow-up. We need to confirm safety. Also, how are we going to define surveillance for these patients, and what strategies are we going to employ to give ourselves confidence in the context of the surgical intervention that may be curative and more definitive, extending beyond the fertility-preserving cohort?
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Lee YJ, 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: SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle.