Lowell L. Hart, MD
Adding the CDK4/6 inhibitor ribociclib to frontline letrozole reduced the risk of disease progression or death by 40% in elderly patients with hormone receptor (HR)–positive, HER2-negative advanced breast cancer, according to a subgroup analysis of the phase III MONALEESA-2 trial presented at the 34th Annual Miami Breast Cancer Conference.
The median progression-free survival (PFS) was not reached (95% CI, 19.3-NR) in the ribociclib arm versus 18.4 months (95% CI, 15-NR) with letrozole alone (HR, 0.608; 95% CI, 0.394-0.937). These data for elderly patients were consistent with the overall study results, in which the median PFS was not reached with the ribociclib combination versus 14.7 months with letrozole alone (HR, 0.56; 95% CI, 0.43-0.72; P
The novel regimen was also well tolerated among the elderly subgroup, with a safety profile similar to the overall study population. Despite a higher rate of patients with an ECOG performance status of 1, the elderly population also had dose interruption and reduction rates consistent with the overall trial results.
In this subgroup analysis, lead author Lowell L. Hart, MD, Florida Cancer Specialists, et al sought to determine whether the addition of CDK4/6 inhibition to standard treatment would improve outcomes in this population.
The multicenter, double-blind phase III MONALEESA-2 trial involved 668 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had not received prior therapy for advanced disease. All patients were treated with the aromatase inhibitor letrozole at a dose of 2.5 mg/day, and investigators randomly assigned study participants to ribociclib at 600 mg/day (3 weeks on/1 week off; n = 334) or placebo (n = 334).
The primary endpoint of the trial was PFS by investigator assessment. Secondary endpoints included overall survival, response rate, and safety. The study ended prematurely after an initial interim data analysis demonstrated a significant benefit in favor of the ribociclib arm.
Among the overall population, 295 patients were aged ≥65 years and 373 patients were aged <65 years. In the elderly patient subgroup, 150 patients were randomized to the ribociclib combination and 145 patients received letrozole alone.
Baseline characteristics were similar between the 2 treatments in the elderly patient subgroup, including mean age (70 in the ribociclib arm vs 71 in the placebo arm), ECOG performance status of 0 (53% vs 55%, respectively), ECOG performance status of 1 (47% vs 46%), bone-only metastatic disease (23% in each arm), visceral metastases (61% vs 59%) and ≥3 metastatic sites (35% vs 37%).
At the time of the analysis, 60% of patients in the ribociclib group remained on study, compared with 53% of the placebo arm. The most common reasons for discontinuation among patients who received ribociclib included progressive disease (22%), adverse event (AE; 9%), physician decision (3%), protocol deviation (2%), and death (1%).
Adverse event–related dose interruptions occurred in 71% of patients receiving ribociclib compared with 13% of patients randomized to placebo. The most common all-grade AEs in elderly patients reported with the ribociclib combination versus letrozole alone included neutropenia (74% vs 5%), nausea (53% vs 29%), fatigue (37% vs 24%), leukopenia (31% vs 4%), alopecia (33% vs 17%), and diarrhea (41% vs 26%).
The authors noted that all-grade anemia rates among patients receiving ribociclib were higher in the elderly population at 26% versus 13% among patients aged <65 years.
All-grade elevated liver enzyme levels were reported for 17% vs 6% of elderly patients in the ribociclib and placebo arms, respectively. Grade 3 prolonged QTcF (>500 ms) occurred in 1 patient in the ribociclib arm.
In November 2016, the FDA granted a priority review to ribociclib for use in combination with letrozole as a frontline therapy for patients with HR+, HER2-negative advanced breast cancer. The agency is scheduled to make its final approval decision by the end of April 2017.<<< View more from the 2017 Miami Breast Cancer Conference