On April 22, 2021, the FDA accelerated the approval of dostarlimab (Jemperli; GlaxoSmithKline), a PD-1 inhibitor, for the treatment of recurrent or advanced endometrial cancer with the mismatch repair-deficient (dMMR) biomarker, as determined by an FDA-approved test, in patients whose disease progressed during or after treatment with a platinum-containing chemotherapy. The FDA had granted dostarlimab a breakthrough therapy designation for this indication.
“This immunotherapy was specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response in this unmet medical need population,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.
Endometrial cancer is the most common gynecologic malignancy in the United States and its prevalence is increasing. Approximately 75% of patients with endometrial cancers are diagnosed at an early stage, but the treatment for advanced or recurrent disease is limited after standard first-line platinum-containing chemotherapy. Approximately 25% to 30% of patients with advanced endometrial cancer have the dMMR biomarker.
The FDA approved dostarlimab based on a single-arm, multicohort clinical trial. Of the 71 patients with dMMR recurrent or advanced endometrial cancer who received dostarlimab in this study, 42.3% had a complete or a partial response. The duration of response was ≥6 months in 93% of the patients with response to therapy with dostarlimab.
The most common side effects reported with dostarlimab included fatigue, nausea, diarrhea, anemia, and constipation. Like other immunotherapies, dostarlimab can cause serious immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Patients with severe or life-threatening infusion-related reactions should stop taking dostarlimab. Pregnant women or those who are breastfeeding should not take dostarlimab.
The FDA may require additional clinical trials to verify the clinical benefit of dostarlimab; these studies are ongoing.