Endometrial cancer incidence and mortality are rising, creating a need for new therapies for advanced or recurrent disease, which has a poor 18.9% 5-year survival rate. Traditional efficacy endpoints often neglect patient quality of life (QoL), leading to the use of a post hoc analysis of the RUBY trial to assess quality-adjusted time without symptoms of disease progression or toxicity of treatment (Q-TWiST), a measure integrating efficacy, safety, and patient QoL.
The RUBY trial, a phase 3 study, compared dostarlimab (an immune checkpoint inhibitor) plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer. Previous results had shown the dostarlimab combination offered statistically significant improvements in progression-free survival and overall survival with an acceptable safety profile.
The Q-TWiST analysis, involving 494 patients, found that the dostarlimab-containing regimen provided a significantly longer mean duration of Q-TWiST compared to the placebo arm across all patient populations (p<.001 for all primary comparisons). In the overall population, the mean Q-TWiST was 24.75 months for the dostarlimab arm versus 20.34 months for the placebo arm, representing a mean difference of 4.41 months and a 17.65% relative improvement. For the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) population, the relative improvement was 21.99%, and for the mismatch repair-proficient/microsatellite stable (MMRp/MSS) population, it was 10.48%. The relative Q-TWiST gain was consistently ≥10%, which is considered clinically relevant. This benefit was primarily driven by an increase in the time without symptoms of disease or toxicity (TWiST) component. The analysis concludes that the benefits of increased survival and delayed disease progression with dostarlimab outweigh the impact of associated adverse events, reinforcing the value of dostarlimab plus chemotherapy as a standard of care for this patient population.