Newly released results from MONALEESA-7 demonstrated that the addition of ribociclib to first-line endocrine therapy dramatically improved progression-free survival (PFS) to nearly two years in pre- and peri-menopausal women with advanced hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer.1 This is the first time for a cyclin-dependent kinase (CDK)4/6 inhibitor to illustrate a clinical benefit as seen in their older counterparts (i.e. post-menopausal).1 The exciting results were presented at the 2017 San Antonio Breast Cancer Symposium (SABCS) by Debu Tripathy, Professor of Medicine and Chair of the Department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center.1
Pre-menopausal breast cancer is biologically distinct from post-menopausal breast cancer.2 Most importantly, the early-onset breast cancer (pre-menopausal) is known to be clinically more aggressive, and it was the leading cause of cancer death in women aged 20-59 years worldwide.2,3 Over the past few years, the combination of CDK4/6 inhibitors with standard endocrine therapy has shown to double the progression-free survival (PFS) in post-menopausal women with HR-positive disease, as compared to endocrine therapy alone.4-6 Nonetheless, the efficacy of CDK4/6 inhibitors in younger women has not yet been evaluated in a dedicated, randomized trial. MONALEESA-7 is the first clinical trial to have the statistical power to shed light on this area.1
In this phase III trial, 672 patients who had not previously received endocrine therapy for advanced disease were randomized to either ribociclib in combination with either tamoxifen or a nonsteroidal aromatase inhibitor (letrozole or anastrozole) plus goserelin (n=335), or placebo plus endocrine therapy (n=337).1
The study met its primary endpoint: ribociclib plus endocrine therapy has led to an impressive PFS of 23.8 months, as compared to 13.0 months in the control arm (HR=0.553; 95% CI: 0.441-0.694; p<0.0001).1 Ribociclib appeared to be effective regardless of its endocrine partner (Table 1).1 “Benefits were also similar among key subgroups including age, race, estrogen-receptor status, liver or lung involvement, disease-free interval or prior chemotherapy for advanced disease,” said Dr. Tripathy.7
The secondary endpoints, including overall response rate (51% vs. 36%), and patient-reported quality-of-life outcomes reflecting global health status, were also in favor of the ribociclib arm. 1 Safety results were generally consistent with those observed in MONALEESA-2, with neutropenia remained the most frequently reported adverse event (AE) in the ribociclib arm (76% vs. 8% in the placebo arm).1 The rate of permanent discontinuation due to AE was generally low (4% vs. 3%).1
Collectively, these findings demonstrated the clinical benefits of ribociclib in combination with endocrine therapies in the pre-menopausal settings. “Now we have CDK4/6 inhibitors in all lines of therapy” said Dr. Tripathy, “The landscape now will be complete for us to be able to look at comparisons and contrasts between these agents… However, we have to keep in mind that these trials are still very young in terms of their follow-up, so we will continue to get further reports that look at survival, [and also] long-term effects.”8
1. Ribociclib Improved Progression-free Survival for Pre- and Perimenopausal Women With Hormone Receptor–positive Advanced Breast Cancer. San Antonio Breast Cancer Symposium Press Releases. 2017 (Accessed December 21, 2017, at https://www.sabcs.org/press-releases).
2. Benz CC. Impact of aging on the biology of breast cancer. Crit Rev Oncol Hematol. 2008;66(1):65–74.
3. Women’s Health Fact Sheet. The World Health Organization 2013 (Accessed December 21, 2017, at http://www.who.int/mediacentre/factsheets/fs334/en/).
4. Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated Results From MONALEESA-2, a Phase III Trial of First-line Ribociclib + Letrozole In Hormone Receptor-positive,
HER2-negative Advanced Breast Cancer. Poster presented at: Annual Meeting of the American Society of Clinical Oncology; June 4, 2017; Chicago,IL. Poster 1038.
5. Palbociclib (IBRANCE). FDA News Release. 2017 (Accessed December 21, 2017, at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm549978.htm).
6. Goetz MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol. 2017;35(32):3638-3646.
7. Ribociclib Effective in Younger Breast Cancer Patients Too. Medscape. 2017 (Accessed December 21, 2017, at https://www.medscape.com/viewarticle/889777_print).
8. Potential in the MONALEESA-7 and MONALEESA-3 Trials. OncLive. 2017 (Accessed December 21, 2017, at http://www.onclive.com/inside-oncology/cdk46-advanced-bc/potential-in-the-monaleesa7-and-monaleesa3-trials).