Adding dostarlimab to chemotherapy can improve outcomes in patients with primary advanced or recurrent endometrial cancer, according to phase 3 results presented at the SGO 2023 Annual Meeting on Women’s Cancer.1
The trial showed that patients who received dostarlimab in combination with carboplatin and paclitaxel had a significant improvement in progression-free survival (PFS), when compared with patients who received the chemotherapy regimen alone.
Though overall survival (OS) data are not yet mature, there was a trend toward an OS benefit with dostarlimab as well.
“Dostarlimab plus carboplatin-paclitaxel represents a new standard of care for patients with primary advanced and recurrent endometrial cancer,” said study presenter Mansoor R. Mirza, MD, of Rigshospitalet, Copenhagen University Hospital in Denmark.
Dr Mirza and colleagues tested this combination in the phase 3 RUBY trial (ClinicalTrials.gov Identifier: NCT03981796). The trial enrolled 494 patients with primary stage III-IV or recurrent endometrial cancer.
Patients were randomly assigned to receive dostarlimab plus carboplatin-paclitaxel (n=245) or placebo plus carboplatin-paclitaxel (n=249). Dostarlimab was given at 500 mg every 3 weeks for 6 cycles. Chemotherapy was also given every 3 weeks for 6 cycles. Patients in the dostarlimab arm could receive dostarlimab maintenance (1000 mg every 6 weeks) for up to 3 years.
Baseline characteristics were generally well balanced between the treatment arms. A minority of patients in both arms had mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors — 21.6% in the dostarlimab arm and 26.1% in the chemotherapy-alone arm.
In the overall study population, the median follow-up was 25.38 months. The median PFS was 11.8 months in the dostarlimab arm and 7.9 months in the chemotherapy-alone arm (hazard ratio [HR], 0.64; 95% CI, 0.507-0.800; P < .0001). The PFS rate at 24 months was 36.1% and 18.1%, respectively.
Among patients with dMMR/MSI-H tumors, the median follow-up was 24.79 months. The median PFS was not reached in the dostarlimab arm and was 7.7 months in the chemotherapy-alone arm (HR, 0.28; 95% CI, 0.162-0.495; P <.0001). The PFS rate at 24 months was 61.4% and 15.7%, respectively.
In the overall population, the median OS was not reached in either arm. Though the OS data were not mature, there was a trend toward longer OS in the dostarlimab arm (HR, 0.64; 95% CI, 0.464-0.870; P = .0021). The 24-month OS rate was 71.3% in the dostarlimab arm and 56.0% in the chemotherapy-alone arm.
Among patients with dMMR/MSI-H tumors, the median OS was not reached in either arm (HR, 0.30; 95% CI, 0.127-0.699). The OS rate at 24 months was 83.3% in the dostarlimab arm and 58.7% in the chemotherapy-alone arm.
Dr Mirza said the safety profile of dostarlimab in combination with carboplatin and paclitaxel was generally consistent with the safety profiles of the individual drugs.
Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 70.5% of patients in the dostarlimab arm and 59.8% of patients in the chemotherapy-alone arm. Serious TEAES occurred in 37.8% and 27.6% of patients, respectively. There were 2 fatal TEAEs deemed related to dostarlimab (myelosuppression and hypovalemic shock).
Results from this study were also published in The New England Journal of Medicine.2
Disclosures: This research was supported by GSK. Dr Mirza disclosed relationships with AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab, Apexigen, Deciphera, and Ultimovacs.
1. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab in combination with chemotherapy for the treatment of primary advanced or recurrent endometrial cancer: A placebo-controlled randomized phase 3 trial (ENGOT-EN6-NSGO/GOG-3031/RUBY). SGO 2023. March 25-28, 2023.
2. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. Published online March 27, 2023. doi:10.1056/NEJMoa2216334