LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB)

Abstract

ML-2 (NCT01958021) is a randomized phase III clinical trial investigating first-line (1L) RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), + letrozole (LET) vs placebo (PBO) + LET in postmenopausal pts with HR+/HER2− ABC. ML-2 previously reported a statistically significant improvement in progression-free survival (PFS; primary endpoint) with RIB + LET vs PBO + LET (HR, 0.56; 95% CI, 0.43-0.72). We report the protocol-specified final analysis of OS (key secondary endpoint). Postmenopausal pts with HR+/HER2− ABC were randomized 1:1 to receive RIB + LET or PBO + LET. Pts were excluded if they received a prior CDK4/6i, chemotherapy (CT), or ET in the advanced setting. OS was evaluated with a stratified log-rank test and summarized using Kaplan–Meier methods. This protocol-specified analysis was planned after 400 deaths. The intention-to-treat population included 668 pts (RIB: 334; PBO: 334). At data cutoff (10 June 2021), 47 pts were still on treatment (RIB: 30 [9.0%]; PBO: 17 [5.1%]) and the median follow-up was 79.7 mo (min, 74.6 mo). Final OS was evaluated after 400 deaths (RIB: 181 [54.2%]; PBO: 219 [65.6%]). RIB + LET showed a significant OS benefit vs PBO + LET (median, 63.9 vs 51.4 mo; HR, 0.76; 95% CI, 0.63-0.93; P=.004) and met the boundary of statistical significance. Estimated 6-year OS rate was 44.2% for RIB vs 32.0% for PBO. Time to first CT (median, 50.6 vs 38.9 mo; HR, 0.74; 95% CI, 0.61-0.91) and CT-free survival (median, 39.9 vs 30.1 mo; HR, 0.74; 95% CI, 0.62-0.89) showed a consistent benefit for RIB vs PBO. Among pts who discontinued study treatment, 87.8% vs 90.2% received a subsequent antineoplastic therapy for RIB vs PBO, respectively, and 21.7% and 34.4% received a subsequent CDK4/6i. No new safety signals were observed. To date, this is the first report of a statistically significant and clinically meaningful OS benefit with a 1L CDK4/6i in postmenopausal pts with HR+/HER2– ABC. After a median follow-up of >6.5 y, median OS improvement was >12 mo for 1L RIB + LET vs PBO + LET.