The FDA expands the indication for dostarlimab-gxly in combination with chemotherapy for endometrial cancer. On August 1, the U.S. Food and Drug Administration (FDA) approved dostarlimab-gxly (brand name Jemperli) in combination with carboplatin and paclitaxel for the treatment of adult patients with primary advanced or recurrent endometrial cancer, followed by maintenance therapy with dostarlimab alone. Previously, dostarlimab was approved in July 2023 for the treatment of primary advanced or recurrent endometrial cancer with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), also in combination with carboplatin and paclitaxel followed by monotherapy.
RUBY Clinical Trial
Efficacy data are based on the RUBY trial (ClinicalTrials.gov, NCT03981796), a randomized, multicenter, double-blind, placebo-controlled study that enrolled 494 patients with primary advanced or recurrent endometrial cancer. Patients were randomized 1:1 to receive either dostarlimab plus carboplatin and paclitaxel (followed by dostarlimab monotherapy) or placebo plus the same chemotherapy (followed by placebo). Stratification factors included MMR/MSI status, prior pelvic external radiotherapy, and disease status (recurrent, primary stage III, or IV).
The primary efficacy endpoint was progression-free survival (assessed by investigators according to RECIST 1.1 criteria for evaluating the efficacy of treatment in solid tumors) in the dMMR/MSI-H patient cohort and the overall population, as well as overall survival in the overall population. Results showed:
Overall survival: The median overall survival in the dostarlimab group was 44.6 months (95% confidence interval [CI] = 32.6 months to non-achievement), and in the placebo group it was 28.2 months (95% CI = 22.1–35.6 months) (hazard ratio [HR] = 0.69, 95% CI = 0.54–0.89, one-sided P = .002).
Progression-free survival: In the overall population, the median progression-free survival in the dostarlimab group was 11.8 months (95% CI = 9.6–17.1 months), and in the placebo group it was 7.9 months (95% CI = 7.6–9.5 months) (HR = 0.64, 95% CI = 0.51–0.80, one-sided P < .0001).
Safety Data
The most common adverse reactions (incidence ≥20%) in the dostarlimab plus chemotherapy group included: anemia, elevated creatinine, peripheral neuropathy, leukopenia, fatigue, nausea, alopecia, thrombocytopenia, elevated glycemia, lymphopenia, neutropenia, abnormal liver function, arthralgia, rash, constipation, diarrhea, decreased albumin, abdominal pain, dyspnea, decreased appetite, elevated amylase, urinary tract infection, and vomiting. Immune-mediated adverse reactions of dostarlimab were consistent with previous reports.
Dosage Recommendations
Recommended dosage:
Combination phase: 500 mg dostarlimab intravenously every 3 weeks (in combination with carboplatin and paclitaxel) for 6 cycles.
Maintenance phase: 1000 mg dostarlimab alone every 6 weeks thereafter until disease progression, intolerable toxicity, or up to 3 years.
If administered on the same day, dostarlimab should be administered first, followed by chemotherapy.
Background of Approval
This review utilized an Assessment Aid voluntarily submitted by the applicant to expedite the FDA's review process. The FDA approved the application three weeks ahead of schedule and granted it Priority Review status.
Disclaimer: This article has not been reviewed by the American Society of Clinical Oncology (ASCO®) and does not necessarily reflect the views or positions of ASCO®.
Source: https://ascopost.com/news/august-2024/fda-expands-endometrial-cancer-indication-for-dostarlimab-gxly-with-chemotherapy/