Journal Article

Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2− advanced breast cancer receiving first-line ribociclib plus fulvestrant

Chakravartty, A., Martín, M., De Laurentiis, M., Chia, S., Zarate, J. P., Slamon, D. J., Beck, J. T., Petrakova, K., Neven, P., Wang, C., Bianchi, G. V., Sonke, G. S., De la Cruz-Merino, L., Wang, Y., Fasching, P. A., Jerusalem, G., Im, S.-A., Nusch, A.

2023

Overview

Background The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2− ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population. Methods Postmenopausal patients with HR+/HER2− ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan–Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615). Results At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50–0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed. Conclusions This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2− ABC.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Advanced breast cancer / Analysis / Antimitotic agents / Antineoplastic agents / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms / Breast Neoplasms - drug therapy / Cancer / Cancer Research / CDK4/6 inhibitor / Chemotherapy / Cyclin-dependent kinase 4 / Endocrine therapy / Epidermal growth factor / ErbB-2 protein / Female / First line / Fulvestrant / Human health sciences / Humans / Medical prognosis / Metastasis / Oncologie / Oncology / Operating systems / Overall survival / Patient outcomes / Patients / Placebos / Post-menopause / Postmenopausal women / Postmenopause / Product development / Proportional Hazards Models / Ribociclib / Sciences de la santé humaine / Surgical Oncology / Survival / Targeted cancer therapy / Womens health