The phase II MAINTAIN trial evaluated the efficacy of adding ribociclib to endocrine therapy in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer and observed a significant survival benefit. The results were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
The combination of cyclin-dependent kinase (CDK) and endocrine therapy is standard of care in HR-positive, HER2-negative metastatic breast cancer. Prior observational data demonstrated a potential benefit of continuing CDK 4/6 inhibitor therapy and switching endocrine therapy once the disease has progressed.
The current investigator-initiated, multicenter, double-blind, placebo-controlled trial evaluated 120 patients (1 was male) with measurable or non-measurable HR-positive, HER2-negative metastatic breast cancer who progressed during CDK 4/6 inhibitor and endocrine therapy. Patients who previously received fulvestrant received exemestane as endocrine therapy and vice versa. Patients who had received neither therapy were randomized based on the investigator’s decision, although fulvestrant was encouraged.
Median patient age was 57 years, and most patients (n=88; 74%) were white. Patients were randomized 1:1 to receive fulvestrant (n=99; 83%) or exemestane (n=20; 17%) with or without ribociclib.
Prior CDK 4/6 therapies included palbociclib (n=100; 84%), ribociclib (n=13; 11%), abemaciclib (n=2; 2%), and palbociclib plus another CDK 4/6 inhibitor (n=4; 3%).
Patients receiving ribociclib in addition to endocrine therapy had a median progression-free survival (PFS; primary outcome) of 5.33 months (95% CI, 3.25-8.12), while those who received endocrine therapy alone had a median PFS of 2.76 months (95% CI, 2.66-3.25; hazard ratio [HR], 0.56; P=.004).
At 6 months, 42% of patients in the ribociclib group remained progression-free compared with 24% of those who received endocrine therapy alone. At 12 months, 25% and 7% of patients, respectively, were progression-free.
The most common hematologic adverse events occurring in patients treated with and without ribociclib were neutropenia (72% vs 15%), anemia (23% vs 22%), and thrombocytopenia (25% vs 5%). The percentage of patients in the ribociclib cohort who experienced infection was 10 (n=6) compared with 5% (n=3) in those who did not receive ribociclib. A total of 2 patients (3%) receiving ribociclib experienced pneumonitis.
“This is the first randomized trial to show the benefit of ribociclib and switching endocrine therapy after progression on a CDK 4/6 inhibitor. Ribociclib plus endocrine therapy led to a statistically significant improvement in PFS compared with placebo plus endocrine therapy in participants with tumor progression following a CDK 4/6 inhibitor,” Kevin Kalinsky, MD, MS, of the Winship Cancer Institute of Emory University, concluded during his presentation at ASCO.
Reference
Kalinsky K, Accordino MK, Chiuzan C, et al. A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial. Abstract #LBA1004. Presented at the 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL.
