Ribociclib for the first-line treatment of advanced hormone receptor-positive breast cancer: a review of subgroup analyses from the MONALEESA-2 trial

Abstract

Endocrine therapy is recommended for patients with hormone receptor-positive (HR+) advanced and metastatic breast cancer without visceral crisis (symptomatic visceral disease). However, many patients experience disease progression during treatment, and most patients eventually develop endocrine resistance. Therefore, it is important to identify treatment options that prolong the effectiveness of first-line endocrine therapies. Ribociclib is an orally bioavailable cyclin-dependent kinase (CDK) 4/6 inhibitor that has been approved for use in combination with an aromatase inhibitor for the treatment of HR+, human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. This approval is based on findings from the MONALEESA-2 study, a double-blind, placebo-controlled, randomized phase 3 trial (NCT01958021) in which first-line therapy with ribociclib + letrozole significantly improved progression-free survival (PFS) compared with placebo + letrozole in patients with HR+/HER2- advanced breast cancer. This review will discuss the overall findings from the MONALEESA-2 study and will provide a summarized analysis of results from the available subgroups in the study by age, visceral metastases, bone-only disease, de novo disease, and prior therapy. On the basis of these data, ribociclib has established itself as a beneficial treatment option for these different populations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01958021 . Registered on 8 October 2013.

Keywords: CDK4/6 inhibitor; Endocrine therapy; HR+/HER2− breast cancer; Hormone receptor-positive; MONALEESA-2; Ribociclib.

Conflict of interest statement

Ethics approval

The MONALEESA-2 trial was conducted in accordance with the Good Clinical Practice guidelines and the provisions of the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

GNH reports receiving personal fees from Novartis during the conduct of the study, and personal fees from Peregrine Pharmaceuticals, personal fees from Lilly, personal fees from Roche, and personal fees from Agendia outside of the submitted work.

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Figures

Fig. 1

MONALEESA-2 subgroup analysis of locally assessed PFS. Data cut-off, 2 January 2017 (Hortobagyi GN 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 the American Society of Clinical Oncology Annual Meeting, Chicago, IL, USA; 2–6 June 2017). CI confidence interval, ECOG PS Eastern Cooperative Oncology Group performance status, ER estrogen receptor, ET endocrine therapy, EXE exemestane, HR hormone receptor, NSAI nonsteroidal aromatase inhibitor, PFS progression-free survival, PgR progesterone receptor, TAM tamoxifen

Fig. 2

Kaplan-Meier curves showing PFS results for a patients aged < 65 years, b patients aged ≥ 65 years, c patients with visceral metastases, d patients with high disease burden, and e patients with de novo disease. CI confidence interval, HR hazard ratio, NR not reached, PFS progression-free survival

Fig. 3

Kaplan-Meier curves showing PFS results for a patients with or without prior CT, and b patients with or without prior ET in MONALEESA-2. CI confidence interval, CT chemotherapy, ET endocrine therapy, HR hazard ratio, NR not reached, PFS progression-free survival