Dr Chase on the FDA Approval of Dostarlimab Plus Chemotherapy in Endometrial Cancer

Dana M. Chase, MD, associate professor, obstetrics and gynecology, Division of Gynecologic Oncology, the University of California, Los Angeles, discusses the significance of the FDA approval of dostarlimab-gxly (Jemperli) plus chemotherapy for patients with primary advanced or recurrent endometrial cancer.

On August 1, 2024, the FDA approved dostarlimab in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab maintenance therapy, for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This approval expanded the regimen’s prior indication for adult patients with mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) primary advanced or recurrent endometrial cancer.

The expanded regulatory decision was supported by findings from part 1 of the phase 3 RUBY trial (NCT03981796), in which patients in the overall population who received the dostarlimab combination (n = 245) achieved a median overall survival of 44.6 months (95% CI, 32.6-not reached) vs 28.2 months (95% CI, 22.1-35.6) with placebo (HR, 0.69; 95% CI, 0.54-0.89; 1-sided P = .002). Furthermore, the median progression-free survival was 11.8 months (95% CI, 9.6-17.1) in the dostarlimab arm compared with 7.9 months (95% CI, 7.6-9.5) in the placebo arm (HR, 0.64; 95% CI, 0.51-0.80; 1-sided P < .0001).

The most common adverse effects occurring in at least 20% of patients who received the dostarlimab regimen included anemia, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, low platelet count, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase, urinary tract infection, and vomiting. 

Endometrial cancers are categorized according to their molecular subtype, and some therapies are more effective in certain patient subgroups based on the disease’s molecular classification, Chase begins. Historically, the use of many endometrial cancer therapies has been limited to specific patient subgroups based on the presence of a biomarker or other molecular classification, she says. However, this expanded indication for dostarlimab widens the eligibility criteria for this agent beyond patients with dMMR/MSI-H disease, Chase concludes.