Ribociclib plus letrozole demonstrated statistically significant improvement in overall survival with the combination in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative advanced or metastatic breast cancer.
Data from the phase 3 MONALEESA-2 trial of ribociclib (Kisqali) plus letrozole demonstrated statistically significant improvement in overall survival (OS) with the combination in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer.1
More than a 12 month increase in OS was demonstrated for ribociclib plus letrozole compared to letrozole alone in the 668- patient study population.
“These positive MONALEESA-2 overall survival data mark tremendous progress in extending the lives of patients living with advanced breast cancer. Achieving overall survival is the gold standard of clinical trials and is particularly impressive in the first-line setting,” said Gabriel N. Hortobagyi, MD, FACP, professor of Medicine, University of Texas MD Anderson Cancer Center, in a press release. “Despite higher subsequent use of CDK4/6 inhibitor therapy in the placebo arm, the ribociclib treatment arm demonstrated a statistically significant overall survival benefit of more than one year. These data solidify ribociclib and letrozole as the preferred CDK4/6 inhibitor combination to offer postmenopausal women with HR+/HER2- advanced disease more time.”
The international, double-blind study, MONALEESA-2 (NCT01958021), enrolled postmenopausal women with advanced breast cancer at 223 trial sites in 29 countries. Patients were randomized and received either ribociclib and letrozole, or letrozole and placebo. None had been previously treated for their advanced disease. Of the participants, 82.2% were white, 7.6% were Asian, 2.5% were Black and others made up 7.6%.
Findings showed median OS among patients within the ribociclib plus letrozole group to be over 5 years (63.9 months) when compared to the placebo group which was 4 years (51.4 months) for the placebo group (HR, 0.76; 95% CI: 0.63-0.93; 2-sided P =.008).
After a median follow-up of 6.6 years, a total of 181 deaths had occurred among the 334 patients (54.2%) in the ribociclib group and 219 among 334 (65.6%) in the placebo group.2 Ribociclib plus letrozole showed a significant OS benefit compared to placebo plus letrozole and there was a 24% reduction in risk of death for patients who received ribociclib plus letrozole as first-line therapy compared to those receiving letrozole alone.
The OS benefit with ribociclib plus letrozole continued to increase over time, with the survival rate of these patients at 52.3% at 5 years which was 8.4% higher than letrozole alone. At 6 years, the survival rate was 44.2%, 12.2% higher than letrozole alone. In the ribociclib plus letrozole group, 21.7% of patients received subsequent treatment with any-line CDK4/6 inhibitor therapy which was fewer than for letrozole alone at 34.4%. After adjusting for subsequent treatment with the use of any-line CDK4/6 inhibitor, significant OS benefit with ribociclib plus letrozole was consistent.
For patients on ribociclib plus letrozole, an additional 1-year delay to subsequent chemotherapy was demonstrated when compared to letrozole alone (50.6 months compared to 38.9 months in the placebo group). At a median of 80 months, this study has the longest reported follow-up for any CDK4/6 inhibitor clinical trial to date.
In regard to safety, no new safety signals emerged, and adverse events were consistent with previously reported phase 3 trial results for ribociclib.