The combination of dostarlimab and chemotherapy demonstrated meaningful improvements in overall survival for the treatment of primary advanced or recurrent endometrial cancer, according to findings from the phase 3 RUBY trial.
Dostarlimab (Jemperli) plus standard-of-care (SoC) chemotherapy followed by dostarlimab monotherapy improved overall survival (OS) in patients with primary advanced or recurrent endometrial cancer compared with placebo and SoC followed by placebo, according to GSK.1
These findings follow the FDA approval of dostarlimab and carboplatin in this patient population earlier this year. Full results from this analysis will be published in a medical journal and presented at a forthcoming scientific meeting.
OS is a coprimary end point in the RUBY trial (NCT03981796). The trial previously met its other primary end point of progression-free survival (PFS) in 2 prespecified subpopulations: mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and mismatch pair proficient (MMRp)/microsatellite stable (MSS). The dMMR/MSI-H and overall patient populations had 72% (HR, 0.28; 95% CI, 0.16-0.50) and 36% (HR, 0.64, 95% CI, 0.51-0.80) reductions in risk of disease progression or death, respectively.
“This is transformative. [RUBY] plus another trial that was done…are consistent and show that adding checkpoint inhibition to the upfront treatment for patients with advanced recurrent endometrial cancer is the new standard of care,” Matthew A. Powell, MD, a professor of obstetrics and gynecology, chief of the division of gynecologic oncology at Washington University School of Medicine, and gynecologic oncologist at Siteman Cancer Center, told Targeted OncologyTM, in an interview.
Regarding safety, the safety and tolerability of this combination regiment is consistent with the known profiles of the individual agents. Treatment-emergent adverse events (TEAEs) in patients receiving dostarlimab and chemotherapy included nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthalgia, constipation, diarrhea, and myalgia.1
The RUBY trial is a phase 3, randomized, double-blind, multicenter study of dostarlimab plus carboplatin-paclitaxel vs placebo and carboplatin-paclitaxel.2 There are 4 arms in the study: 2 active comparators and 2 placebo comparators. The first active comparator arm received dostarlimab plus carboplatin followed by dostarlimab. The second active comparator arm received dostarlimab and carboplatin followed by dostarlimab and niraparib (Zejula). Both placebo comparator arms received placebo and carboplatin followed by placebo.
Secondary end points of the RUBY trial include PFS by blinded independent central review (BICR), objective response rate by BICR and investigator assessment, duration of response by BICR and investigator assessment, patient-reported outcomes (PROs) in the European Quality-of-Life Scale, PROs in the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire and endometrial cancer module, changes in baseline vital signs, number of TEAEs, and ECOG performance status scores.
Patients were eligible to participate if they were female, over the age of 18, had histologically or cytologically proven endometrial cancer with recurrent or advanced disease, had a low potential for cure by radiation or surgery alone, and an ECOG performance status of 0 or 1. Patients were not eligible to participate if they had more than 1 recurrence of endometrial cancer, received treatment with an anti-PD-1 or anti-PD-L agent, or a concomitant malignancy.2
“With today’s headline results from part 1 of the phase 3 RUBY trial, dostarlimab plus chemotherapy has become the only immunotherapy combination to show a survival benefit in this broader patient population in this treatment setting,” said Hesham Abdulla, senior vice president, global head oncology, research and development, GSK, said in a press release.1