First-line (1L) ribociclib (RIB) plus letrozole (LET) for postmenopausal women with hormone receptor-positive (HR+), HER2- advanced breast cancer (ABC): MONALEESA-2 long-term safety results.

Abstract

1078 Background: In the phase III MONALEESA-2 study (NCT01958021), 1L treatment (Tx) with RIB (cyclin-dependent kinase 4/6 inhibitor) plus LET significantly prolonged PFS vs placebo (PBO) + LET in patients (pts) with HR+/HER2– ABC (HR 0.56; P<0.0001). In the primary publication (data cutoff, Jan 2016), the median duration of exposure was 13.0 mo (RIB + LET) and 12.4 mo (PBO + LET), and the most common all-grade adverse events (AEs) in the RIB + LET arm were neutropenia (74.3%), nausea (51.5%), infections (50.3%), fatigue (36.5%), and diarrhea (35.0%; Hortobagyi GN, et al. N Engl J Med. 2016;375:1738-48). Here we present long-term safety data from MONALEESA-2. Methods: Pts received either RIB + LET (n=334) or PBO + LET (n=330). AEs were graded per CTCAE v4.03. Results: As of data cutoff (Oct 2018), 79 (24%) pts (RIB + LET) and 39 (12%) pts (PBO + LET) remained on Tx. The median duration of exposure was 20.2 mo (range, 0-54) for RIB + LET and 14.1 mo for PBO + LET, and 30% and 17%, respectively, had ≥ 36 mo of exposure. Neutropenia was the most common exposure-adjusted any-grade AE of special interest (AESI) in the RIB + LET arm (Table). AEs were the most common reason for RIB dose reductions (56.6%) and interruptions (73.4%). Discontinuations due to AEs occurred in 19.2% and 4.2% of pts in the RIB + LET and PBO + LET arms, respectively, and the most common AEs leading to discontinuation in the RIB + LET arm were increased ALT (4.5%), GI disorders (3.3%), and increased AST (2.7%). Prolonged QT led to dose interruption in 0.9% of patients (no discontinuations), and the additional follow-up did not reveal any sudden deaths related to prolonged QT interval beyond the 1 identified in the primary analysis. Conclusions: AEs occurring with 1L RIB + LET in postmenopausal pts with HR+/HER2– ABC were manageable and the safety profile was comparable to that in the primary report. Clinical trial information: NCT01958021. [Table: see text]