Nivolumab Shows Promising Efficacy in dMMR Uterine and Ovarian Cancers

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A phase 2 trial demonstrated that nivolumab is effective and has a manageable safety profile in patients with mismatch repair deficiency uterine or ovarian cancers.

Gynecologic Cancer Illustration: © Crystal Light - stock.adobe.com

Gynecologic Cancer Illustration: © Crystal Light - stock.adobe.com

A single-arm, phase 2 trial (NCT03241745) evaluating nivolumab in patients with mismatch repair deficiency (dMMR) uterine or ovarian cancers, the coprimary end points of overall response rate (ORR) and progression-free survival at 24 weeks (PFS24) were met.1

Among the 35 patients included in the study, the ORR was 58.8% (97.5% CI, 40.7%-100%). The PFS24 rate was 64.7% (97.5% CI, 46.5%-100%), meeting the prespecified end points of the trial.

PD-1 inhibitors are currently approved for the treatment of gynecologic cancers with dMMR. However, predictors of response remain elusive. As a result, this study sought to test the safety of nivolumab and find out what effects, if any, the agent has on individuals and their risk of gynecologic cancer.

In the experimental arm of the trial, nivolumab was given intravenously at a dose of 480 mg once every 4 weeks. Treatment continued until time of disease progression or until development of unacceptable toxicity, whichever came first.2

Enrollment was open to patients with a histologically confirmed diagnosis of metastatic or recurrent uterine cancer, including endometrial carcinoma, carcinosarcoma, clear cell carcinoma, leiomyosarcoma, undifferentiated sarcoma, and high-grade endometrial stromal sarcoma. The tumor must be confirmed as either microsatellite instability-high, dMMR, or hypermutated, defined as ≥20 somatic mutations in the tumor, and patients must have had at least 1 prior lines of cytotoxic treatment for advanced disease. Further, patients were required to have measurable disease by RECIST 1.1 criteria, no known central nervous system metastases, and an ECOG performance status 0 to 1.

In addition to the coprimary end points of ORR and PFS24, secondary end points of the study were overall survival (OS), disease control rate (DCR), duration of response (DOR) and safety. Exploratory end points evaluated were biomarkers and molecular correlates of response.

Additional findings from the study showed that the DCR was 73.5% (95% CI, 55.6%-87.1%).1 At the median follow-up of 42.1 months (range, 8.9-59.8 months), the median OS was not reached. At 1 year, the OS was 79% (95% CI, 60.9%-89.4%).

For safety, 32 patients (91%) had a treatment-related adverse event (TRAE). These included arthralgia in 10 patients (29%), fatigue in 10 (29%), pain in 10 (29%) and pruritis in 10 (29%). Most of these TRAEs were deemed grade 1 or grade 2. Additionally, 10 patients (29%) had a grade 3 or grade 4 TRAE, and no grade 5 events were observed.

REFERENCES:
1. Friedman CF, Manning-Geist BL, Zhou Q, et al. Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses. Nat Med. 2024;30(5):1330-1338. doi:10.1038/s41591-024-02942-7
2. A study of nivolumab in selected uterine cancer patients. ClinicalTrials.gov. Updated April 4, 2024. Accessed June 21, 2024. https://clinicaltrials.gov/study/NCT03241745?tab=table
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