MONALEESA 3: Ribociclib Provides Significant PFS in Postmenopausal Women With ER+/HER- Advanced Breast Cancer Regardless of Prior Endocrine Therapy

With a greater than 40% decreased risk for disease progression, the combination of ribociclib and fulvestrant was significantly better than that of placebo and fulvestrant for postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer regardless of whether or not they had received one prior endocrine therapy, according to data presented at the American Society of Clinical Oncology 2018 Annual Meeting in Chicago, Illinois.¹ These data are from the Mammary Oncology Assessment of LEE011’s (Ribocliclib’s) Efficacy and Safety (MONALEESA) 3 study.

The phase 3 double-blind, placebo-controlled study randomly assigned 726 patients in a 2:1 ratio to receive either ribociclib and fulvestrant or placebo and fulvestrant.

Patients received ribociclib 600 mg/day at a 3-week on and 1-week off schedule or placebo. All patients received fulvestrant 500 mg daily.

Median duration from randomization to data cut-off was 20.4 months.

MONALEESA 3 met its primary endpoint of progression-free survival (PFS). With a hazard ratio (HR) of 0.59, median PFS was 20.5 months for patients receiving ribociclib and 12.8 months for those receiving placebo (P = 4.1 x 10^-7). Blinded independent review confirmed these findings.

With fulvestrant being antiestrogenic, it was important to determine if these benefits were sustained in patients who had received prior endocrine therapy. Indeed, PFS benefits were also seen whether or not patients had received prior endocrine therapy.

Risk for disease progression was reduced by 42% (HR: 0.58; 95% confidence interval [CI]: 0.42-0.80) for patients with no prior endocrine therapy and by 43% (HR: 0.57; 95% CI: 0.43-0.74) for patients who had received up to 1 line of prior endocrine therapy.

Objective response rate (complete and partial responses) was also significant for patients receiving ribociclib: 41% compared with 29% for placebo (P = .003) as was clinical benefit rate (complete and partial responses and those with stable disease): 69% compared with 60% for placebo (P  = .015).

Adverse events (vs placebo) in 30% of patients or more receiving ribociclib were neutropenia (70% vs 2%), nausea (45% vs 28%), and fatigue (31% vs 33%). Grade 3/4 (vs placebo) neutropenia (54% vs 0%), ALT increase (9% vs 1%), and AST increase (6% vs 1%) was also reported at a higher incidence in patients receiving ribociclib.

With the combination of ribociclib and letrozole (an aromatase inhibitor) already approved for this patient population, MONALEESA 3 suggests that the combination of ribociclib and fulvestrant may also be another treatment option. 

Read more of Cancer Therapy Advisor‘s coverage of the American Society of Clinical Oncology (ASCO) 2018 meeting by visiting the conference page.

Reference

1. Slamon DJ, Neven P, Chia SKL, et al. Ribociclib (RIB) + fulvestrant (FUL) in postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2 –) advanced breast cancer (ABC): Results from MONALEESA-3. J Clin Oncol. 2018: 36, (suppl; abstr 1000). Presented at 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.