In the phase II MAINTAIN trial reported in the Journal of Clinical Oncology, Kevin Kalinsky, MD, MS, and colleagues found that a switch in endocrine therapy plus continued CDK4/6 inhibitor treatment with ribociclib was associated with improved progression-free survival in patients with hormone receptor–positive, HER2-negative metastatic breast cancer who had had disease progression on previous endocrine therapy and CDK4/6 inhibitor treatment.

Kevin Kalinsky, MD, MS

Study Details

In the U.S. multicenter double-blind trial, 119 patients were randomly assigned between May 2016 and December 2021 to switching endocrine therapy plus ribociclib at 600 mg once daily for 21 days on/7 days off (n = 60) or switching endocrine therapy plus placebo (n = 59). Patients switched from prior endocrine therapy to fulvestrant or to exemestane if fulvestrant was the prior endocrine therapy. Fulvestrant was given at 500 mg intramuscularly on cycle 1 day 1 and 15 and then day 1 every 4 weeks. Exemestane was given at 25 mg once daily. Overall, fulvestrant was the endocrine therapy backbone in 99 patients (83%). Prior CDK4/6 inhibitor therapy was palbociclib in 103 patients and ribociclib in 14. The primary endpoint was progression-free survival. 

Progression-Free Survival

Median duration of follow-up was 18.2 months (interquartile range = 10.1­–28.8 months). Median progression-free survival was 5.29 months (95% confidence interval [CI] = 3.02–8.12 months) in the ribociclib group vs 2.76 months (95% CI = 2.66–3.25 months) in the control group (hazard ratio [HR] = 0.57, 95% CI = 0.39–0.85, P = .006). Rates at 6 and 12 months were 41.2% vs 23.9% and 24.6% vs 7.4%, respectively. Hazard ratio estimates were similar for patients who previously received palbociclib (0.58, 95% CI = 0.38–0.89) and those who previously received ribociclib (HR = 0.50, 95% CI = 0.15–1.70).

In an exploratory analysis, among 49 vs 50 patients receiving fulvestrant, median progression-free survival was 5.29 months (95% CI = 2.96–8.12 months) in the ribociclib group vs 2.76 months (95% CI = 2.66–3.25 months) in the control group (HR = 0.60, 95% CI = 0.39–0.94).  Among 11 vs 9 patients receiving exemestane, median progression-free survival was 5.36 months (95% CI = 3.02–14.50 months) in the ribociclib group vs 3.06 months (95% CI = 1.84–5.95 months) in the control group (HR = 0.41, 95% CI = 0.14–1.24).

Adverse Events

The most common grade 3 or 4 adverse events in the ribociclib group were neutropenia (40% vs 2% in control group) and infection (5% vs 0%); the most common in the control group was increased aspartate transaminase (7% vs 2%). Any-grade neutropenia, anemia, and thrombocytopenia occurred in 72% vs 15%, 23% vs 22%, and 25% vs 5% of patients. Grade 1 or 2 pneumonitis occurred in two patents in the ribociclib group. One patient in each group had grade ≥ 2 QT interval prolongation. Deaths considered related to treatment occurred in two patients in the ribociclib group (due to sepsis, neutropenia, and disease progression in one, and pneumonia in the other) and in one patient in the control group (due to pneumonia).

The investigators concluded, “In this randomized trial, there was a significant progression-free survival benefit for patients with hormone receptor–positive/HER2-negative metastatic breast cancer who switched endocrine therapy and received ribociclib compared with placebo after previous CDK4/6 inhibition and different endocrine therapy.”

Dr. Kalinsky, of the Department of Hematology and Medical Oncology, Winship Cancer Institute at Emory University, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Novartis Pharmaceuticals and the Breast Cancer Research Foundation. For full disclosures of the study authors, visit ascopubs.org.