|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
In an exploratory analysis with an extended follow-up, ribociclib plus fulvestrant showed consistent superior overall survival (OS) benefit in postmenopausal patients with hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2-) metastatic breast cancer, according to the research presented by Dennis J. Slamon, MD, PhD, of the David Geffen School of Medicine at the University of California, Los Angeles in Santa Monica, during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
Deregulation of the cyclin dependent kinase (CDK) 4/6 pathway in HR+ breast cancers is implicated in resistance to endocrine therapy. Ribociclib is an inhibitor of CDK4 and CDK6 that is approved for patients with HR+/HER2- advanced breast cancer.
The randomized double-blind, placebo-controlled phase 3 MONALEESA trial (ClinicalTrials.gov Identifier: NCT02422615) evaluating ribociclib with fulvestrant in postmenopausal patients with HR+/HER2- metastatic breast cancer had demonstrated a significant progression-free survival (PFS) and OS benefit over fulvestrant alone (median, not reached vs 40.0 months; hazard ratio [HR], 0.72; 95% CI, 0.57-0.92; P =.00455).
“MONALEESA-3 remains the only randomized trial evaluating a CDK4/6 inhibitor to demonstrate an OS benefit in postmenopausal patients with HR+/HER2- advanced breast cancer treated in the first-line setting,” said Dr Slamon. He reported the updates of long-term survival benefits of ribociclib after an additional median follow-up of 16.9 months and characterization of post-progression endpoints including time to second objective disease progression (PFS2), time to chemotherapy (CT), and CT-free survival.
Postmenopausal patients with HR+/HER2- metastatic breast cancer were randomly assigned at a 2:1 ratio to receive ribociclib with fulvestrant (484 patients) or fulvestrant with placebo (242 patients) in first-line and second-line settings.
At the data cutoff (October 30, 2020), the median follow-up was 56.3 months, at which point 68 patients (14.0%) were still on ribociclib with fulvestrant and 21 patients (8.7%) were on fulvestrant with placebo treatment.
During the extended follow-up in the total study population, ribociclib with fulvestrant continued to provide more than 1 year OS benefit (53.7 months) compared with fulvestrant plus placebo (41.5 months) (hazard ratio [HR], 0.73; 95% CI, 0.59-0.90). In the first-line setting, patients treated with ribociclib plus fulvestrant had prolonged OS compared with patients who received fulvestrant plus placebo (median, not reached vs 51.8 months; hazard ratio [HR] 0.64; 95% CI, 0.46-0.88). In the second-line setting, ribociclib plus fulvestrant provided a 6 month longer median OS compared with placebo plus fulvestrant (median, 39.7 vs 33.7 months; hazard ratio [HR], 0.78; 95% CI, 0.59-1.04). A consistent OS benefit was observed across most subgroups compared with the intent-to-treat (ITT) population.
Ribociclib plus fulvestrant prolonged median OS compared with placebo plus fulvestrant in patients who were sensitive to endocrine therapy (ET) as well as those who were resistant to ET.
The PFS2, time to CT, and CT-free survival for the ITT population were more favorable in the ribociclib plus fulvestrant group than in fulvestrant plus placebo group. Ribociclib plus fulvestrant was associated with a nearly 20-month delay in the use of subsequent CT. CT-free survival was prolonged by approximately 10 months with ribociclib plus fulvestrant compared with fulvestrant alone. A longer PFS2 was observed in patients receiving ribociclib plus fulvestrant (median, 37.4 months) compared with fulvestrant plus placebo (median, 28.1 months).
Adverse events were consistent with those in the previous analyses of MONALEESA-3 with no new safety signals observed during the extended follow-up.
“The findings of the robust and clinically meaningful OS benefit with ribociclib plus fulvestrant compared [with] fulvestrant alone over a nearly 5 year follow-up period in postmenopausal patients with HR+/HER2- metastatic breast cancer supports the use of ribociclib in these populations in the first-line and second-line settings,” said Dr Slamon.
Disclosure: This research study was funded by Novartis Pharmaceuticals Corporation. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.
Slamon DJ, Neven P, Chia SKL, et a1. Updated overall survival (OS) results from the phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2- advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). J Clin Oncol. 2021;39:(suppl 15; abstr 1001). doi:10.1200/JCO.2021.39.15_suppl.1001