A long-term follow-up study has confirmed the results of the phase-III MONALEESA-7 trial, the first randomized clinical trial of its kind to compare a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus endocrine therapy with endocrine therapy plus placebo in premenopausal or perimenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) advanced breast cancer.

The follow-up study concluded that ribociclib (Kisqali; Novartis) plus endocrine therapy continued to demonstrate a clinically relevant overall survival benefit compared with endocrine therapy alone in this patient population over more than four years. 

In a presentation to the 2020 San Antonio Breast Cancer Symposium (abstract PD2-04), the international, multicenter team of researchers behind the trial explained that MONALEESA-7  (NCT02278120) previously demonstrated statistically significant improvements in overall survival by adding ribociclib to endocrine therapy compared with endocrine therapy plus placebo. At the conclusion of the trial, patients in the placebo arm were allowed to cross over to ribociclib therapy.

“Longer follow-up,” they wrote, “allows for more events to further characterize the long-term survival benefits.” In the current analysis, the investigators performed an exploratory update of overall survival after a minimum of four years, which they said is some 20 months longer than their last report. 

MONALEESA-7 included premenopausal or perimenopausal women with HR+/HER2- advanced breast cancer who had received endocrine therapy in the (neo)adjuvant setting or ≤1 prior line of chemotherapy. These patients were randomized to receive ribociclib or placebo plus goserelin (Zoladex; TerSera Therapeutics), with either a nonsteroidal aromatase inhibitor (letrozole or anastrozole) or tamoxifen. Individuals who had received a prior CDK4/6i or endocrine therapy in the advanced setting were excluded. 

In the follow-up study, the researchers updated overall survival endpoints, and also evaluated and summarized such post-progression endpoints as progression-free survival, time to chemotherapy, and chemotherapy-free survival. 

According to lead author Debu Tripathy, MD, of The University of Texas MD Anderson Cancer Center, in Houston, Texas, the median follow-up for the long-term analysis was 53.5 months (minimum 46.9 months). Updated analyses of overall survival demonstrated continued benefit with ribociclib plus endocrine therapy (median 58.7 months) compared with placebo plus endocrine therapy (median 48.0 months), yielding a hazard ratio of 0.76 (95% confidence interval: 0.61-0.96). 

Similar results were observed with ribociclib plus a nonsteroidal aromatase inhibitor (median 58.7 months) versus those receiving placebo plus a nonsteroidal aromatase inhibitor (median 47.7 months; HR 0.80; 95% CI: 0.62-1.04). 

As Table 1 demonstrates, all secondary endpoints favored patients receiving ribociclib, whether or not they also received a nonsteroidal aromatase inhibitor.

With respect to patients who discontinued study treatment, 77.3% in the ribociclib-endocrine therapy group received subsequent antineoplastic therapy, compared with 78.1% of their counterparts in the placebo-endocrine therapy group. Similarly, 12.9% and 26.1% of patients in the two groups, respectively, received a subsequent line of CDK4/6i. 

Finally, 15 patients in the placebo arm crossed over to the ribociclib group following unblinding, and prior to disease progression. 

 The findings were met with enthusiasm by Karen Gelmon, MD, Professor of Medicine at the University of British Columbia in Vancouver, Canada. “This data with improved overall survival is very compelling for the medical community when making decisions about the optimal treatment for pre- and perimenopausal patients with advanced or metastatic breast cancer,” she said in a statement.