Treatment with dostarlimab combined with carboplatin and paclitaxel (CP) confers sustained long-term progression-free survival (PFS) and overall survival (OS) benefits on patients with primary advanced or recurrent deficient mismatch repair and microsatellite instability-high (dMMR/MSI-H) endometrial cancer, as shown by the results of the phase III RUBY trial.
At 4-year follow-up, the “median PFS and OS were not reached with dostarlimab plus CP in the dMMR/MSI-H population from RUBY,” said lead study author Dr Vladyslav Sukhin, Grigoriev Institute for Medical Radiology and Oncology National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine.
“The high rate of durable remission suggests the potential for curative intent with dostarlimab plus CP in this patient population,” Sukhin added.
A total of 118 patients were randomly allocated to receive either dostarlimab plus CP (n=53) or placebo plus CP (n=65) for six cycles, followed by dostarlimab or placebo monotherapy every 6 weeks for up to 3 years or until disease progression. The authors performed a descriptive analysis of PFS and OS in patients with primary advanced and recurrent dMMR/MSI-H endometrial cancer.
In the post hoc analysis, Sukhin and colleagues reported the clinical characteristics, treatment duration, and RECIST v1.1 responses at 1-year landmark interval among patients in the dostarlimab arm achieving complete response (CR) and those achieving long-term (≥3 years) disease control.
Survival benefits
At a median follow-up of 55.6 months, patients treated with dostarlimab plus CP showed continuous PFS (4-year rate, 57.9 percent, 95 percent confidence interval [CI], 42.3‒70.6; hazard ratio [HR], 0.30, 95 percent CI, 0.17‒0.52) and OS (4-year rate, 72.8 percent, 95 percent CI, 58.5‒82.9; HR, 0.34, 95 percent CI, 0.19‒0.63) relative to those on placebo. [ESMO Gyn 2026, abstract 71RO]
“Only four new progression events were reported with an additional 2.5 years of follow-up since the primary PFS analysis (23 Sep 2022),” Sukhin said.
Nearly a third of patients treated with dostarlimab plus CP (n=17, 32.1 percent) achieved CR, of whom three later progressed and one died. Only one patient who achieved CR at 1 year had documented progression at the 4-year landmark.
“Additionally, sustained long-term clinical benefit was observed across disease responses,” Sukhin said.
Furthermore, 17 (32.1 percent) patients in the dostarlimab arm achieved partial response (PR), 10 (18.9 percent) had a stable disease (SD), and two (3.8 percent) had progressive disease (PD). In the placebo arm, 11 (16.9 percent) and 26 (40.0 percent) achieved CR and PR, while 12 (18.5 percent) and four (6.2 percent) had SD and PD, respectively.
“A low incidence of progression was reported in patients who achieved CR,” Sukhin said. Nonetheless, “[l]ong-term benefit was observed across all patients with disease control and was not restricted to those patients with CR.”
Earlier studies have shown that dostarlimab is the only regimen combined with CP that has yielded significant and clinically meaningful PFS and OS in patients with primary advanced or recurrent endometrial cancer, with improved quality of life in the dMMR/MSI-H population. [Engl J Med 2023;388:2145-2158; Ann Oncol 2024;35:728-738]