Adding ribociclib to everolimus and letrozole failed to improve survival across unselected endometrial cancer patients, according to a phase 2 clinical trial published in Nature Communications.
Researchers evaluated the triplet regimen against everolimus and letrozole alone in the randomized trial, registered as NCT03008408. Progression-free survival showed no statistically significant difference across all-comers, yielding a hazard ratio of 0.78 (95% CI 0.4–1.4, p = 0.38). Overall survival similarly showed no significant difference, posting a hazard ratio of 0.8 (95% CI 0.4–1.5, p = 0.46). Objective response rates measured 44.1% in the experimental arm compared to 25.7% in the control arm (p = 0.11), while treatment discontinuation from toxicity reached 8.6% versus 11.4% (p = 0.22).
Patient subgroups showed divergent outcomes. Among participants who received prior endocrine therapy, the objective response rate was 61.5% in the experimental arm compared to 0.0% in the control arm (p < 0.001). Within the experimental cohort, patients with CTNNB1-mutated tumors experienced improved progression-free survival (HR 0.27, 95% CI 0.1–0.7, p = 0.006) and overall survival (HR 0.24, 95% CI 0.1–0.7, p = 0.004) compared to those with non-mutated tumors.
Jeffrey A. How and Shannon N. Westin conducted the research alongside collaborators from The University of Texas MD Anderson Cancer Center and the University of North Carolina School of Medicine. Novartis provided drug supplies and research funding for the investigator-initiated study without participating in study design, data collection, or reporting. The researchers previously presented interim findings at the Society of Gynecologic Oncology Annual Meeting in Tampa in March 2023 and updated results at the International Gynecologic Cancer Society Annual Global Meeting in Cape Town in November 2025.
