Adding ribociclib, a CDK4/6 inhibitor, to letrozole significantly improved progression-free survival (PFS) in postmenopausal women with advanced, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR-positive/HER2-negative) breast cancer, according to results of a phase III trial.
“Women living with metastatic breast cancer will be on treatment for the rest of their lives, so it is critical to find treatment options that effectively delay progression,” said Gabriel N. Hortobagyi, MD, of the University of Texas MD Anderson Cancer Center in Houston, according to a press release. Hortobagyi presented results of the MONALEESA-2 trial at the European Society for Medical Oncology (ESMO) 2016 Congress, held October 7–11 in Copenhagen, Denmark.
The study, which was also published simultaneously in the New England Journal of Medicine, randomized 668 postmenopausal women with HR-positive/HER2-negative recurrent or metastatic breast cancer to either ribociclib plus letrozole or placebo plus letrozole.
Patients were excluded if they had received any previous CDK4/6 inhibition therapy, or other systemic chemotherapy or endocrine therapy specifically for advanced disease. The median age of patients was 62 years; 58.8% had visceral metastases, and 22% had only bone metastases. At the study cutoff date, 195 patients in the ribociclib and 154 patients in the placebo group were still on treatment; the median follow-up period was 15.3 months.
A preplanned interim analysis was triggered after at least 211 patients had disease progression or died. At that point, the trial met its primary efficacy endpoint: the median PFS was not reached in the ribociclib group, vs 14.7 months in the placebo group, for a hazard ratio for progression of 0.56 (95% CI, 0.43–0.72; P = 3.29 × 10-6). After 18 months the PFS rate was 63% in the ribociclib group compared with 42.2% in the placebo group.
Response rates were also better with the study drug, at 40.7% compared with 27.5% in the placebo patients (intention-to-treat population). Overall survival data have not yet matured, and the study remains blinded to wait for those results.
The most common grade 3 or 4 adverse events included neutropenia (59.3% of the ribociclib patients vs 0.9% of placebo patients), leucopenia (21% vs 0.6%, respectively), hypertension (9.9% vs 10.9%, respectively), and increased alanine aminotransferase levels (9.3% vs 1.2%, respectively). More patients in the ribociclib group (7.5%) than in the placebo group (2.1%) discontinued treatment due to adverse events.
“The MONALEESA-2 results show the combination of [ribociclib] plus letrozole represents a significant step forward in the management of HR-positive metastatic breast cancer and, if approved, would be a major addition to the treatment options these patients have,” Hortobagyi said.