The combination of ribociclib and endocrine therapy resulted in improved progression-free survival (PFS) over placebo plus endocrine therapy in a phase III trial of premenopausal women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer.
“Treatment recommendations for premenopausal patients [have] been extrapolated from studies in the postmenopausal population, making broad assumptions that treatment outcomes would be similar without conclusive evidence,” wrote study authors led by Debu Tripathy, MD, of the University of Texas MD Anderson Cancer Center in Houston. The MONALEESA-2 trial found that ribociclib along with letrozole offered improved PFS in postmenopausal advanced breast cancer patients; the new MONALEESA-7 study tested ribociclib plus tamoxifen or a nonsteroidal aromatase inhibitor (NSAI) in a premenopausal population.
The trial was a double-blind randomized study conducted at 188 centers in 30 countries. In total, it included 672 patients (335 ribociclib, 337 placebo); the median age in the two groups was 43 and 45 years, respectively, and more than half of patients in both groups were white. All patients had confirmed HR-positive, HER2-negative advanced breast cancer. The results were published in Lancet Oncology.
After a median follow-up period of 19.2 months, the median PFS was 23.8 months in ribociclib patients and 13.0 months in placebo patients, for a hazard ratio (HR) of 0.55 (95% CI, 0.44–0.69; P < .0001). The results were similar in the subgroups of patients receiving tamoxifen and an NSAI, and benefit with ribociclib was seen across a variety of other patient subgroups.
The overall survival data were not yet mature. A total of 89 deaths had been recorded, including 43 in the ribociclib group (13%) and 46 in the placebo group (14%).
At 6 months, 35.1% of ribociclib patients had a response to the therapy, compared with 24.6% of placebo patients. The median duration of response was 21.3 months with the study drug, and 17.5 months with placebo. The median time to definitive deterioration as measured by health status and quality-of-life questionnaires was not reached in the ribociclib group, and it was 21.2 months in the placebo group, for an HR of 0.70 (95% CI, 0.53–0.92; P = .004).
Serious adverse events were reported in 18% of ribociclib patients and in 12% of placebo patients. Among the most common grade 3/4 adverse events with ribociclib were neutropenia, leukopenia, and increased alanine aminotransferase.
“These data complement those obtained in the postmenopausal population, further supporting the benefit of inhibitors of CDKs 4 and 6 in combination with endocrine therapy for advanced, HR-positive breast cancer, and suggest that the combination of ribociclib with endocrine therapy could represent a new treatment option for premenopausal patients,” the authors concluded.