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.

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 MONALEESA-3.

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 QA progression-free survival (QAPFS), QAOS, and QA TWiST (Q-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.