Dostarlimab-gxly Plus Chemotherapy Receives Expanded Approval for Endometrial Cancer
Expert Perspectives · Lyn Brook · 2024-08-02
The FDA has granted an expanded approval to dostarlimab-gxly (Jemperli, GSK) plus carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adult patients with primary advanced or recurrent endometrial cancer. Previously, the FDA approved dostarlimab-gxly with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).
Why it matters: “Dostarlimab is an immune checkpoint inhibitor that targets the programmed cell death 1 receptor,” wrote Mansoor R. Mirza, MD, Chief Oncologist at the Department of Oncology, Rigshopitalet, the Copenhagen University Hospital, Denmark, and colleagues, in their published results of the RUBY trial (NCT03981796), on which approval was based. “The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer.”
What they studied: Efficacy and safety were measured in the phase 3, double-blind, placebo-controlled trial in which 494 patients with primary advanced or recurrent endometrial cancer were randomized 1:1 to receive either dostarlimab-gxly plus carboplatin and paclitaxel, followed by dostarlimab-gxly, or placebo with carboplatin and paclitaxel, followed by placebo. Stratification for randomization was based on MMR/MSI status, prior external pelvic radiotherapy, and disease status—recurrent, primary stage III, or primary stage IV.
The primary efficacy outcomes measured were progression-free survival, assessed via investigator using RECIST v1.1, in the dMMR/MSI-H and overall populations, and overall survival in the overall population.
What they found: A statistically significant overall survival improvement was observed in the overall population. The median overall survival in the dostarlimab-gxly arm was 44.6 months compared with the placebo arm at a median of 28.2 months. The median progression-free survival observed in the overall population was 11.8 months in the dostarlimab-gxly arm compared with 7.9 months in the placebo arm.
Adverse events: The most common adverse events experienced in ≥20% of patients receiving dostarlimab-gxly with carboplatin and paclitaxel were anemia, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, low platelets, increased glucose, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin, abdominal pain, dyspnea, decreased appetite, increased amylase, urinary tract infection and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported for dostarlimab-gxly. See dostarlimab-gxly full prescribing information for complete adverse event information.
Conclusion: “Dostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population,” concluded Dr. Mirza.
Instructions: The recommended dosage of dostarlimab-gxly is 500 mg every three weeks for six cycles plus carboplatin and paclitaxel, followed by 1,000 mg monotherapy every six weeks until disease progression or unacceptable toxicity, or up to three years. When administered on the same day as chemotherapy, dostarlimab-gxly should be administered first.