Randomized phase 2 trial of everolimus plus letrozole with or without ribociclib for recurrent endometrial cancer

A randomized phase 2 trial at MD Anderson Cancer Center (Houston, TX) evaluated everolimus plus letrozole with (experimental arm) or without (control arm) ribociclib among patients with recurrent endometrial cancer (EC). The primary endpoint was progression-free survival (PFS), and secondary endpoints were toxicity, overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). For all-comers, there were no significant differences in PFS (HR 0.78; 95% CI 0.4-1.4), OS (0.8; 0.4-1.5), ORR (44.1% versus 25.7%; p=0.11), or toxicity-related treatment discontinuations (8.6% versus 11.4%; p=0.22). Among patients with prior endocrine therapy, ORR was higher in the experimental arm (61.5% versus 0; p<0.001). Within the experimental arm, CTNNB1_mut tumors were associated with improved PFS (HR 0.27; 95% CI 0.1-0.7) and OS (0.24; 0.1-0.7) compared to those with non-CTNNB1_mut tumors. The authors conclude that addition of ribociclib to everoliums plus letrozole may improve efficacy in patients with prior endocrine therapy and cases with CTNNB1_mut tumors.