Adding ribociclib to letrozole significantly improves progression-free survival for postmenopausal women with metastatic hormone receptor (HR)-positive breast cancer, compared with hormone therapy alone, a study published in the New England Journal of Medicine has shown.1,2

Because women with metastatic breast cancer will need some kind of therapy for the rest of their lives, therapies that will delay disease progression are needed for this patient population. Furthermore, all breast cancers become resistant to endocrine therapy at some point.

In the international double-blind study, MONALEESA-2 (Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer; Identifier NCT01958021), researchers sought to determine the efficacy of combining a CDK4/6 inhibitor (ribociclib) with an aromatase inhibitor (letrozole) for progression-free survival, overall survival, overall response rate, and safety, compared with hormone therapy alone.

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For the phase 3 trial, researchers randomized 668 postmenopausal women with advanced breast cancer to receive either ribociclib and letrozole, or letrozole and placebo. Patients were followed for a median 15.3 months. None of the women had received prior treatment for their advanced disease.

At data cut-off, median progression-free survival in the ribociclib arm was not reached; it was 14.7 months in the placebo arm. Results showed a 44% improvement in progression-free survival with ribociclib and letrozole as front-line therapy, with an overall response rate for the ribociclib arm among those patients with measurable disease of 52.7% vs 37.1% in the placebo arm.

Although serious adverse events were reported in less than 5% of patients, side effects were higher in the ribociclib arm vs the placebo arm, respectively, including neutropenia (59% vs 1%) and leukopenia (21% vs 1%). 

Most side effects were managed with dose interruption and reduction. Discontinuation rates were 7.5% in the ribociclib arm and 2.1% in the placebo arm.

“These findings could represent a paradigm shift in the future medical management of this patient population,” reported the researchers.2

The researchers are designing follow-up adjuvant trials with ribociclib. In addition, researchers will investigate the efficacy of ribociclib in younger, premenopausal women with breast cancer.

This trial is sponsored by Novartis. Ribociclib was granted Breakthrough Therapy Designation by the US FDA in August 2016. 


1. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016 Oct 8. doi: 10.1056/NEJMoa1609709. [Epub ahead of print]

2. MD Anderson-led study finds ribociclib improves progression-free survival for women with metastatic breast cancer [news release]. Copenhagen, Denmark: The University of Texas MD Anderson Cancer Center; October 8, 2016. October 11, 2016.