Pooled efficacy analysis of first-line ribociclib (RIB) plus endocrine therapy (ET) in HR+/HER2: Advanced breast cancer (ABC)

Abstract

Background: In 3 Phase III trials, RIB (cyclin-dependent kinase 4/6 inhibitor) + various ET partners demonstrated longer progression-free survival (PFS) vs placebo (PBO) + ET in patients (pts) with HR+/HER2- ABC. Using pooled trial data from the MONALEESA-2 (ML-2; all patients), ML-3 (ET-naïve subgroup only), and ML-7 (NSAI subgroup only) trials, we further evaluate efficacy in ET-naive pts here. Methods: ML-2 and ML-3 enrolled ET-naive postmenopausal pts with ABC to receive PBO or RIB+ study-designated ET, letrozole (ML-2) or fulvestrant (ML-3). In ML-7, ET-naive premenopausal pts with ≤1 line of chemotherapy for ABC received RIB or PBO + goserelin + nonsteroidal aromatase inhibitor or tamoxifen. The primary endpoint was locally assessed PFS. Secondary endpoints included clinical benefit rate (CBR) and overall response rate (ORR). Results: Data were pooled from 1530 pts (including 34% with de novo metastatic disease) treated with RIB +ET (n=820) or PBO + ET (n=710). Median follow-up time for PFS was 15.1 (ML-2), 16.5 (ML-3), and 13.0 (ML-7) months. Addition of RIB to ET prolonged PFS vs PBO (median, 25.3 vs 15.6 months; HR, 0.57 95% CI, 0.49-0.66]). The PFS benefit of RIB +ET over PBO + ET was observed in most pt subgroups, including those defined by age, race, baseline ECOG performance status, presence of visceral or bone metastases, de novo metastatic disease, and prior chemotherapy. ORR and CBR were both improved in the RIB arm vs the PBO arm, and the estimated probabilities of tumor response for RIB vs PBO were 16.0% vs 10.0% at 2 months, 35.2% vs 22.6% at 6 months, and 42.3% vs 28.8% at 12 months (Table). Conclusions: The addition of RIB to several ET partners consistently demonstrated longer PFS and higher response rates vs PBO + ET in this pooled population. This very large data set (> 1500 pts) supports RIB-based ET as an option for a diverse population of pre- and postmenopausal pts with ET-naive HR+/HER2- ABC. (Table Presented).