Image Credit: © barinovalena
– stock.adobe.com
First-line treatment with dostarlimab-gxly (Jemperli) plus carboplatin and paclitaxel prolonged time to first subsequent therapy (TFST) and time to second subsequent therapy (TSST) vs placebo plus chemotherapy in patients with primary advanced or recurrent endometrial cancer regardless of age, according to findings from a post hoc analysis of part 1 of the phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial (NCT03981796).¹
Results presented during the 2025 ESMO Gynecological Cancers Congress showed that, in the overall patient population (n = 494), the median TFST increased from 10.2 months (95% CI, 9.1-10.9) with the placebo regimen (n = 249) to 15.3 months (95% CI, 12.3-20.1) with the dostarlimab regimen (n = 245; HR, 0.63; 95% CI, 0.51-0.78). The median TSST with the dostarlimab regimen increased to 31.3 months (95% CI, 24.6-40.8) from 19.9 months (95% CI, 16.3-23.1) with the placebo regimen (HR, 0.67; 95% CI, 0.53-0.85).
Among those 70 years of age or older (n = 145), TFST and TSST were prolonged by 8.7 and 8.0 months, respectively, with the dostarlimab (n = 74) vs placebo (n = 71) regimens. For patients younger than 70 years of age (n = 349), the median TFST and TSST were prolonged by 2.9 and 12.6 months, with these respective regimens (n = 171; n = 178).
Comparable results were seen in the mismatch repair–proficient (pMMR)/microsatellite stable (MSS) patient population (n = 376). In this patient population, dostarlimab plus chemotherapy (n = 192) increased the median TFST from 10.2 months (95% CI, 9.0-10.8) with the placebo regimen (n = 184) to 12.7 months (95% CI, 11.4-17.1), translating to a HR of 0.73 (95% CI, 0.58-0.92). The median TSST improved from 18.7 months (95% CI, 15.3-22.0) with the placebo regimen to 26.8 months (95% CI, 22.1-32.6) with the dostarlimab combination (HR, 0.73; 95% CI, 0.57-0.94).
Among those 70 years or older (n = 110), the median TFST and TSST were prolonged by 5.8 and 4.9 months, respectively, with dostarlimab (n = 57) vs placebo (n = 53). Patients younger than 70 years of age (n = 266) saw a 2.3- and 10.8-month increase, respectively, in median TFST and TSST with the dostarlimab (n = 135) and placebo (n = 131) regimens.
“With more than 3 years of follow-up, these results demonstrate the efficacy and tolerability of frontline dostarlimab plus carboplatin and paclitaxel in patients aged 70 years or older…,” Ilana Cass, MD, and colleagues wrote in a poster presentation of the data. Cass is a professor of Obstetrics and Gynecology and chair of the Department of Obstetrics and Gynecology at Geisel School of Medicine, Dartmouth University, in Lebanon, New Hampshire.
Study Background and Design
Previously reported data from RUBY supported the July 2023 FDA approval of dostarlimab in combination with carboplatin and paclitaxel, followed by dostarlimab monotherapy, for adult patients with primary advanced or recurrent endometrial cancer that is dMMR or microsatellite instability high (MSI-H).2
The randomized, double-blind, multicenter study enrolled patients with primary advanced or recurrent endometrial cancer, who were randomly assigned to receive either dostarlimab plus carboplatin and paclitaxel every 3 weeks, followed by dostarlimab monotherapy every 6 weeks for no more than 3 years; or placebo plus carboplatin and paclitaxel, followed by placebo monotherapy.1 Patients were also categorized as younger than 70 years of age vs 70 years of age or older.
The study’s dual primary end points were progression-free survival (PFS) and overall survival (OS) in the overall population, and PFS in the mismatch repair–deficient/MSI-H patient population. Safety served as a secondary end point, and a subgroup analysis of safety according to age group was performed as a post hoc analysis.
In the current analysis, investigators evaluated TFST, TSST, and safety by age subgroup in the overall and pMMR/MSS patient populations from RUBY. The data cutoff for this post hoc analysis was September 22, 2023, at the time of the second interim analysis.
TFST and TSST were defined as the time from randomization to either the initiation of the first dose of the first or second subsequent anticancer therapy, respectively; or death by any cause.
Additional Subgroup Efficacy and Safety Data
All patients in both treatment arms experienced treatment-emergent adverse effects (TEAEs) regardless of age subgroup, and safety outcomes in both age subgroups were consistent with that of the overall patient population.
Similar increases in safety-related events for both treatment arms were observed in patients aged 70 years or older vs younger than 70 years. The incidence of grade 3 or higher TEAEs in patients aged 70 years or older increased by 5.5% and 8.5% in the dostarlimab and placebo arms, respectively, vs those younger than 70 years. Increases in the rates of serious AEs (+7.5% in the dostarlimab arm; +16.0% the placebo arm), treatment-related immune-related AEs (+4.3%; +4.8%), and TEAEs that led to the discontinuation of dostarlimab or placebo (+6.8%; +0.5%) were also observed.
The rate of immune-related adverse effects (irAEs) related to dostarlimab was higher in the 70 years of age or older subgroup (43.7%) vs the younger than 70 years subgroup (39.4%); the incidence of placebo-related irAEs similarly increased between these respective subgroups (19.7%; 14.9%).
However, death due to TEAEs in the dostarlimab arm was numerically lower in patients 70 years or older (1.4%) vs patients younger than 70 years (2.4%). No deaths due to TEAEs occurred in the placebo arm for either age subgroup.
“Together with the statistically significant PFS and OS benefits and favorable long-term safety profile, these findings support the frontline use of dostarlimab plus carboplatin and paclitaxel as a standard of care in all patients with primary advanced or recurrent endometrial cancer regardless of age,” Cass and coauthors concluded.
Disclosures: Cass had nothing to disclose.
Reference
- Cass I, Herrstedt J, Jackson A , et al. Time to next treatment by age subgroup in patients with primary advanced or recurrent endometrial cancer (pA/rEC) in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. ESMO Open. 2025;10(suppl 5):105175. doi:10.1016/j.esmoop.2025.107
- Jemperli (dostarlimab) plus chemotherapy approved in the US as the first new frontline treatment option in decades for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GlaxoSmithKline. July 31, 2023. Accessed July 10, 2025. https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-chemotherapy-approved-in-us-for-new-indication/