3-year RUBY data support add-on dostarlimab as frontline Tx for endometrial cancer

At the second interim analysis of part 1 of the phase III RUBY study, updated duration of response (DoR) findings suggest that women with primary advanced or recurrent endometrial cancer who have achieved a response with the combination regimen comprising dostarlimab and carboplatin-paclitaxel (CP) have substantially improved DoR.

“The substantial DoR improvement was seen across all three populations, including the mismatch-repair proficient/microsatellite stable (MMRp/MSS) population, wherein median DoR was increased by 1.4 times,” said the investigators.

In the overall cohort, median DoR was longer by 4.4 months in the dostarlimab vs the placebo arm (10.6 vs 6.2 months). There was about a threefold increase in the proportion of participants with DoR ≥24 months in the investigational vs the placebo arm (30.7 percent vs 12 percent). The Kaplan-Meier (KM) probability of having a response at 2 years was also up by almost threefold (37 percent vs 14.3 percent). [SGO 2025, abstract 232]

Subgroup analyses, irAEs

In the MMRp/MSS subgroup, about two-thirds of participants with evaluable disease at baseline achieved a response (68.1 percent [dostarlimab] and 63.4 percent [placebo]). The median DoR was longer in the dostarlimab vs the placebo arm (8.6 vs 6.3 months).

Compared with the placebo arm in the MMRp/MSS subgroup, the dostarlimab arm had more participants with a DoR ≥24 months (22.5 percent vs 12.7 percent), and the KM probability of having a response at 2 years was twice as high (27.6 percent vs 14.7 percent).

Among those with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) disease, the proportion of participants with evaluable disease at baseline who achieved a response was higher in the experimental vs the comparator arm (79.6 percent vs 69 percent). The median DoR was not reached in the former and 5.4 months in the latter.

Moreover, in the dMMR/MSI-H subset, the fraction of patients with DoR ≥24 months was nearly sixfold higher in the dostarlimab vs the placebo arm (53.8 percent vs 10 percent), and the KM probability of having a response at 2 years was about five times higher in the former vs the latter arm (62.2 percent vs 13.2 percent).

Overall, there were few immune-related adverse events (irAEs) beyond 24 months. “The most common dostarlimab- or placebo-related irAEs in the overall cohort (experienced by ≥5 percent of patients throughout the entire trial duration) were hypothyroidism, arthralgia, increased alanine aminotransferase, and rash,” the investigators said.

Supports initial findings

Dostarlimab + CP has been approved for the treatment of women with primary advanced or recurrent endometrial cancer in the US, EU, and other countries, the researchers noted. The approvals were based on the initial results of RUBY part 1, which showed a significant survival benefit with the combination regimen as opposed to placebo in this patient setting. [N Engl J Med 2023;388:2145-2158; Ann Oncol 2024;35:728-738]

“At the first interim analysis, a substantial increase in DoR was observed with dostarlimab vs placebo in the overall population after a median follow-up of 25.4 months,” they said. In this second interim analysis, they report updated DoR and safety data with over 3 years of follow-up.

In RUBY part1 , 494 women were randomized 1:1 to receive dostarlimab 500 mg or placebo with CP Q3W for six cycles, followed by dostarlimab 1,000 mg or placebo alone Q6W for up to 3 years. A majority (n=376) of the participants had MMRp/MSS disease, while the remainder comprised the dMMR/MSI-H cohort. About 71 percent of women in the overall dostarlimab cohort who had evaluable disease at baseline achieved a response; the corresponding rate in the placebo arm was 64.8 percent.

At this second interim analysis, the median follow-up duration in the overall population was 37.2 months.