Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial

Abstract

Purpose: Ribociclib plus endocrine therapy (ET) demonstrated a statistically significant progression-free survival and overall survival (OS) benefit in the phase III MONALEESA-7 trial of pre-/perimenopausal patients with hormone receptor (HR)-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). The median OS was not reached in the ribociclib arm in the protocol-specified final analysis; we hence performed an exploratory OS and additional outcomes analysis with an extended follow-up (median, 53.5 months).

Patients and methods: Patients were randomized to receive ET [goserelin plus nonsteroidal aromatase inhibitor (NSAI) or tamoxifen] with ribociclib or placebo. OS was evaluated with a stratified Cox proportional hazard model and summarized with Kaplan-Meier methods.

Results: The intent-to-treat population included 672 patients. Median OS was 58.7 months with ribociclib versus 48.0 months with placebo [hazard ratio = 0.76; 95% confidence interval (CI), 0.61-0.96]. Kaplan-Meier estimated OS at 48 months was 60% and 50% with ribociclib and placebo, respectively. Subgroup analyses were generally consistent with the OS benefit, including patients who received NSAI and patients aged less than 40 years. Subsequent antineoplastic therapies following discontinuation were balanced between the ribociclib (77%) and placebo (78%) groups. Use of cyclin-dependent kinase 4/6 inhibitors after discontinuation was higher with placebo (26%) versus ribociclib (13%). Time to first chemotherapy was significantly delayed with ribociclib versus placebo. No drug-drug interactions were observed between ribociclib and either NSAI.

Conclusions: Ribociclib plus ET continued to show significantly longer OS than ET alone in pre-/perimenopausal patients, including patients aged less than 40 years, with HR+/HER2- ABC with 53.5 months of median follow-up (ClinicalTrials.gov, NCT02278120).

©2021 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.

OS. A, All patients. B, Patients who received an NSAI. C, Patients who received tamoxifen. mo, months; PBO, placebo; RIB, ribociclib.

Figure 2.

Exploratory analyses of OS in subgroups. ECOG, Eastern Cooperative Oncology Group; ER, estrogen receptor; mOS, median overall survival; NR, not reached; PGR, progesterone receptor; mo, months. aER and PGR receptor status ++ means that patients were positive for both estrogen and progesterone receptors. bPatients who relapsed within the first 2 years of (neo)adjuvant ET. cPatients who received prior ET and did not experience relapse within the first 2 years of (neo)adjuvant ET.

Figure 3.

Time to first subsequent chemotherapy and chemotherapy-free survival. A, Time to first subsequent chemotherapy. B, Chemotherapy-free survival. CFS, chemotherapy-free survival; mo, months; PBO, placebo; RIB, ribociclib; TTC, time to chemotherapy.

Figure 4.

PFS2, progression-free survival following receipt of subsequent therapy. mo, months; PBO, placebo.