Impact of ribociclib (RIB) dose modifications (mod) on overall survival (OS) in patients (pts) with HR+/HER2- advanced breast cancer (ABC) in MONALEESA(ML)-2.

Abstract

1017 Background: The phase 3 ML-2, -3, and -7 trials all demonstrated consistent and statistically significant OS benefit with RIB (starting dose: 600 mg/d 3 wk on/1 wk off) vs PBO in pts with HR+/HER2− ABC. RIB dose mod (reductions and/or interruptions) when needed did not impact OS benefit with RIB + endocrine therapy (ET) in previous analyses of ML-3/-7. Here we present data on the effect of RIB dose mod on OS in postmenopausal pts with HR+/HER2− ABC in ML-2. Methods: ML-2 (NCT01958021) enrolled postmenopausal pts randomized 1:1 to first-line RIB + letrozole (LET) or PBO + LET. Landmark (LM) analyses of OS were performed to evaluate the association between dose reductions (yes vs no) and OS. Multiple LM times were considered to determine the sensitivity of the findings. As an alternative to LM analysis, a Cox proportional hazards model with a time-varying covariate was performed. Two time-dependent variables, dose reduction (with/without mod from 600 mg starting dose) and relative dose intensity 2 (RDI2), were included in the respective model as covariates to explore the association with OS. To account for differences in time to first dose mod, RDI2 reflects the post–dose mod period. Median (m) OS was obtained using a modified Kaplan-Meier method. Results: At data cutoff (June 10, 2021; m follow-up, 49.35 [range, 0-86.7] mo), 209 of 334 pts (62.6%) had ≥ 1 RIB dose reduction and 125 of 334 (37.4%) had 0 RIB dose reduction. LM analyses by dose reduction are presented (Table). mOS was 66.0 (95% CI, 57.6-75.7) mo in pts with ≥ 1 RIB dose reduction vs 60.6 (95% CI, 42.5-79.2) mo in pts with no RIB dose reductions (HR, 0.87 [95% CI, 0.65-1.18]). RDI2 was classified according to tertile: low (< 64.27%), medium (64.27%-95.86%), and high (> 95.86%). In pts with low, medium, and high RDI2, mOS was 62.6 (95% CI, 50.0-80.7) mo, 63.9 (95% CI, 48.8-not reached [NR]) mo, and 65.3 (95% CI, 50.5-NR) mo, respectively (HR low vs high, 0.99 [95% CI, 0.69-1.42]; HR medium vs high, 0.97 [95% CI, 0.62-1.38]). Conclusions: In this exploratory analysis of ML-2, OS benefit was maintained in pts with HR+/HER2− ABC who required mod from the recommended starting dose of RIB (600 mg/d 3 wk on/1 wk off). No relationship was observed between OS and RIB dose reduction or RDI2; OS benefit with RIB was observed in all groups. Clinical trial information: NCT01958021. [Table: see text]