Quality-Adjusted Survival with Ribociclib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Postmenopausal Women with HR±HER2-Advanced Breast Cancer in the MONALEESA-3 Trial

This exploratory analysis of the MONALEESA-3 trial demonstrated that ribociclib plus fulvestrant resulted in significantly improved quality-adjusted progression-free survival and quality adjusted time without symptoms or toxicity; quality adjusted overall survival was numerically greater with ribociclib treatment. These findings strengthen the previously reported survival benefits associated with ribociclib treatment and support the use of ribociclib as recommended by clinical guidelines. Background: MONALEESA-3 demonstrated an overall survival (OS) benefit for ribociclib plus fulvestrant (R+F) in postmenopausal women with hormone receptor (HR) positive, HER2 negative advanced breast cancer (ABC). This study estimated quality-adjusted (QA) survival outcomes for patients receiving R+F vs. placebo (P)+F in MONALEESA3. Methods: Kaplan-Meier OS was partitioned into health states: (1) toxicity (TOX)-time spent with grade 3 -4 adverse events before progression (DP); (2) progression (PROG)=time between DP and death; and (3) time without symptoms or toxicity (TWiST)=time not in TOX or PROG. QA time was calculated by combining estimated mean time in each health state with treatment-group specific health-state utility values estimated using EQ-5D-5L questionnaire. Outcomes included OA progression-free survival (QAPFS), QAOS, and QA TWiST (0-TWIST). Q-TWiST was calculated with health-state utility values for TOX and PROG defined relative to TWIST. Results: Mean PFS and OS were significantly greater with R+F vs. P+F (difference 0.56 and 0.19 years). Mean time in TOX and TWiST were greater with R+F; mean time in PROG was greater with P+F. QAPFS was 0.45 years (95% CI 0.27-0.63) greater with R+F than P+F (P <.001). QAOS was numerically greater with R+F vs. P+F (0.16 years, 95% CI 0.07 -0.45, P = .0569). Q-TWiST was 0.23 years greater with R+F (95% CI 0.07 -0.45, P = .0069). In a sensitivity analysis using an estimate of disutility for PROG, the difference in QAOS was 0.23 years (95% CI 0.08-0.41, P = .0022). Conclusion: R+F in postmenopausal women with HR+/HER2- ABC improves QAPFS, resulting in clinically important improvements in Q-TWiST and may improve QAOS. (C) 2021 Elsevier Inc. All rights reserved.