Updated Overall Survival Results From MONALEESA-3 Show Improved Overall Survival in Patients With HR-Positive/HER2-Negative Breast Cancer

Get Permission

In an updated analysis of the phase III MONALEESA-3 trial, which included postmenopausal patients with advanced/metastatic hormone receptor (HR)-positive, HER2-negative breast cancer, first-line treatment with ribociclib plus fulvestrant lengthened overall survival by approximately 16 months vs fulvestrant alone, according to data presented at the ESMO Breast Cancer Congress 2022 by Patrick Neven, MD, PhD, of the Universitaire Ziekenhuizen Leuven in Belgium (Abstract LBA4). After 70.8 months of follow-up for previously untreated patients, median overall survival was 67.6 months with ribociclib/fulvestrant vs 51.8 months with fulvestrant alone (hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.50–0.90). 

“We have an impressive benefit…. Ribociclib combined with fulvestrant demonstrated the longest median overall survival observed for a first-line population in the phase III setting of advanced breast cancer,” Dr. Neven said.

“In the 5-year landmark analysis, one out of seven patients are alive without an overall survival event,” he continued. “Not only is survival improved, but also secondary endpoints, including progression-free survival–2, chemotherapy-free survival, and time to chemotherapy. These results stress the importance of combining these agents [inhibitors of cyclin-dependent kinases (CDK) 4 and 6] with endocrine treatment for advanced breast cancer.”

Ribociclib combined with fulvestrant demonstrated the longest median overall survival observed for a first-line population in the phase III setting of advanced breast cancer.
— Patrick Neven, MD, PhD

Tweet this quote


MONALEESA-3 evaluated ribociclib plus fulvestrant in 726 patients with advanced/metastatic HR-positive, HER2-negative breast cancer who were either previously untreated or treated with no more than one prior line of therapy. Dr. Neven presented an updated analysis that focused on the 365 patients treated in the first-line setting.

The study found that ribociclib plus fulvestrant achieved a median overall survival of 67.6 months compared to 51.8 months for fulvestrant alone, resulting in a 33% reduction in death (HR = 0.673, 95% CI = 0.504–0.899).  With extended follow-up, the estimated survival rate at 5 years was 56.5% vs 42.1%. Additionally, 16.5% of patients receiving the doublet were still undergoing treatment at this longer follow-up, compared to 8.6% receiving only fulvestrant.

Previous Analyses

The current analysis builds upon previous findings for MONALEESA-3. In the final protocol-specified overall survival analysis, after 39.4 months of follow-up, ribociclib was associated with a statistically significant overall survival benefit over placebo (HR = 0.72, P = .00455).

A further exploratory analysis at 56.3 months of follow-up confirmed the overall survival benefit, showing a median overall survival of 53.7 months with ribociclib vs 41.5 months with placebo (HR = 0.73, 95% CI = 0.59–0.90) in the intent-to-treat population. However, median overall survival was not reached in the subset of patients receiving treatment in the first line, which accounted for about half the population. This subset was the focus of the current analysis presented at the ESMO Breast Cancer Congress 2022, which was performed after a median of 70.8 months, offering an additional 2.5 years of follow-up.

Secondary Endpoints Improved

Patients treated with first-line ribociclib plus fulvestrant compared to fulvestrant alone experienced more than 1.5 years’ additional delay to subsequent use of chemotherapy: 49.2 months vs 29.0 months (HR = 0.62, 95% CI = 0.481–0.810). Time to second progression (time from random assignment to first disease progression after discontinuing treatment) was also notably prolonged, from 34.6 months with fulvestrant to 50.7 months with ribociclib/fulvestrant (HR = 0.64, 95% CI = 0.49–0.84). Time to chemotherapy was also delayed (HR = 0.57, 95% CI = 0.42–0.79), he reported. 

No new safety signals were observed. The frequency of adverse events remained generally consistent with prior analyses of the study.

Disclosure: For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.