The FDA has approved dostarlimab plus chemotherapy for patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient, as determined by an FDA-approved test, or microsatellite instability-high.
The FDA has approved frontline dostarlimab (Jemperli) in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab, for adult patients primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H).1
The approval is supported by data from an interim analysis from part 1 of the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO trial. At a median follow up of over 25 months, the 2-year progression-free survival (PFS) rate among patients with dMMR/MSI-H who received the immune-checkpoint inhibitor (n = 53) was 61.4% (95% CI, 46.3%-73.4%). Among patients who received placebo plus chemotherapy (n = 65), the rate was 15.7% (95% CI, 7.2%-27.0%), yielding an HR of 0.28 (95% CI, 0.16-0.50; P < .001).2
“As a clinician, I celebrate the practice-changing potential of adding [dostarlimab] to chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer who have had limited treatment options,” Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial, stated in a press release from GSK, the drug’s manufacturer. “Based on the results from the RUBY clinical trial, I look forward to the addition of [dostarlimab] to chemotherapy becoming a new standard of care for patients.”
Approximately 15% to 20% of patients who receive an endometrial cancer diagnosis will have advanced disease. Moreover, it is estimated that 20% to 29% of all patients with endometrial cancers are dMMR/MSI-H. The approval marks the first immunochemotherapy combination to be approved in the frontline setting for these patients. According to the trial investigators, the increased mutational burden of dMMR/MSI-H tumors make them potentially vulnerable to anti–PD-1 and anti–PD-L1 therapies.
The recommended dose of dostarlimab, in combination with carboplatin and paclitaxel, for dMMR or MSI-H primary advanced or recurrent endometrial cancer, is 500 mg every 3 weeks for 6 doses. This is to be followed by a 1000 mg dose of dostarlimab alone every 6 weeks. The injection is available as a 500 mg/10 mL solution in a single-dose vial.3
Dostarlimab’s prescribing information lists warnings for immune-mediated adverse events, infusion-related reactions, allogeneic hematopoietic stem cell transplantation complications, and embryo-fetal toxicity. The most common adverse events to occur in this patient population include rash, diarrhea, hypothyroidism, and hypertension. The most common grade 3 or 4 laboratory abnormalities include decreased neutrophils, decreased hemoglobin, decreased white blood cell count, decreased lymphocytes, increased glucose, decreased sodium, and decreased platelets.
“The endometrial cancer community is thrilled by today’s news, which changes the treatment paradigm for a population with long-term unmet needs,” Wenora Johnson, President of the Board of Directors for Facing Our Risk of Cancer Empowered (FORCE), said in the release. “As an endometrial cancer survivor, I know how much this approval offers hope for patients with primary advanced or recurrent dMMR/MSI-H endometrial cancer.”1