Commentary
Video
Emily Hinchcliff, MD, MPH, discusses the addition of dostarlimab to standard-of-care chemotherapy in patients with advanced/recurrent endometrial cancer.
“The real remaining question is: Can we further delineate [the MMR] subgroups? [These subgroups are] not homogeneous and represents this large opportunity for further study. [This] brings up the question of treatment sequencing in the recurrent setting.”
Emily Hinchcliff, MD, MPH, gynecologic oncologist, assistant professor, obstetrics and gynecology, Northwestern University Feinberg School of Medicine, discusses findings from the second interim analysis of overall survival (OS) from the phase 3 RUBY trial (NCT03981796), which evaluated the addition of dostarlimab-gxly (Jemperli) to standard-of-care (SOC) chemotherapy in patients with advanced or recurrent endometrial cancer.
The interim analysis, conducted at 51% OS maturity, revealed a statistically significant HR of 0.69 (95% CI, 0.54-0.89) with the combination regimen vs placebo plus chemotherapy for the overall trial population, Hinchcliff begins. She notes that the most substantial OS benefit was observed in the mismatch repair–deficient (dMMR) subgroup, which had an OS HR of 0.32 (95% CI, 0.17-0.63), which was consistent with findings from the initial analysis, a result she describes as unprecedented in this patient population.
In contrast, the OS HR in the MMR-proficient (pMMR) subgroup showed a trend toward significance for the combination over chemotherapy alone but did not achieve the same magnitude of benefit observed in the dMMR group. Hinchcliff highlights the heterogeneity within MMR populations and emphasizes the need for further research to delineate these subgroups and explore additional combination therapies that may enhance outcomes.
A notable observation from the study was the high rate of subsequent immunotherapy use in both arms, with over 38.2% of patients in the placebo arm and 17.1% of those in the dostarlimab-containing arm receiving immunotherapy following disease progression. Despite this, the OS benefit with dostarlimab plus chemotherapy remained robust, raising important questions about treatment sequencing and optimal management strategies in the recurrent setting, according to Hinchcliff.
Hinchcliff also underscores the importance of refining treatment approaches for dMMR patients, who now benefit from the integration of immunotherapy into first-line care. She notes that these findings prompt critical considerations about the next steps in managing recurrent disease, particularly as immunotherapy becomes entrenched in the SOC.
Hinchcliff concludes that the RUBY trial results reinforce the need for continued research into subgroup-specific therapies and treatment sequencing strategies.