Randomized Phase II Trial of Endocrine Therapy With or Without Ribociclib After Progression on Cyclin-Dependent Kinase 4/6 Inhibition in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer: MAINTAIN Trial

Abstract

PURPOSE Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) improves progression-free survival (PFS) and overall survival (OS) in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer (MBC). Although preclinical and clinical data demonstrate a benefit in changing ET and continuing a CDK4/6i at progression, no randomized prospective trials have evaluated this approach. METHODS In this investigator-initiated, phase II, double-blind placebo-controlled trial in patients with HR+/HER2– MBC whose cancer progressed during ET and CDK4/6i, participants switched ET (fulvestrant or exemestane) from ET used pre-random assignment and randomly assigned 1:1 to the CDK4/6i ribociclib versus placebo. PFS was the primary end point, defined as time from random assignment to disease progression or death. Assuming a median PFS of 3.8 months with placebo, we had 80% power to detect a hazard ratio (HR) of 0.58 (corresponding to a median PFS of at least 6.5 months with ribociclib) with 120 patients randomly assigned using a one-sided log-rank test and significance level set at 2.5%. RESULTS Of the 119 randomly assigned participants, 103 (86.5%) previously received palbociclib and 14 participants received ribociclib (11.7%). There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo. CONCLUSION In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2– MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET.

Abemaciclib plus endocrine therapy versus chemotherapy after progression on prior palbociclib in HR+/HER2‐ metastatic breast cancer: A single center real‐world study in China

“…However, MAINTAIN trial offered the initial evidence that using ribociclib and switching ET had significantly improved the median PFS compared to placebo plus switching ET after progression on a prior CDK4/6 inhibitor (86.5% palbociclib) (5.29 months vs. 2.76 months). 39 Whereas, continuing palbociclib plus switching ET after progression on palbociclib did not show clinical benefit in the phase II PACE trial 40 and PALMIRA trial. 41 These inconsistent findings imply that the rechallenge strategy of CDK4/6 inhibitors might not be suitable for all CDK4/6 inhibitors.…”

“…To date, three randomized phase II trials have been reported to evaluate this approach. 39 , 40 , 41 Only the MAINTAIN trial demonstrated positive results, 39 whereas the PACE trial and PALMIRA trial showed negative results. 40 , 41 Therefore, more data are needed to determine the sequence and principle of reuse of CDK4/6 inhibitor.…”

ABC7 Consensus: Assessment by a German Group of Experts

“…From the German perspective, "TbP" might be an option due to side effects. In the MAINTAIN trial [11], CDK4/6 inhibitor plus switching endocrine monotherapy was superior to endocrine monotherapy and showed a benefit in median PFS (HR 0.57; p = 0.006). The German experts also point to the numerous treatment alternatives after ET-based first-line therapy such as elacestrant in case of ESR1 mutation, alpelisib/fulvestrant for patients with PIK3CA mutation, as well as everolimus plus ET or fulvestrant as monotherapy [1].…”

Abemaciclib-based therapy versus tucidinostat-based therapy in patients with HR+HER2− metastatic breast cancer after palbociclib progression: insights and challenges from a comparative cohort study in China

“…The MAINTAIN trial demonstrated a significant progression-free survival (PFS) benefit for patients with HR + /HER2 – MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i. In contrast, the PACE trial revealed no evident PFS advantage, whereas the PALMIRA trial illustrated that maintaining a regimen of palbociclib alongside endocrine therapy did not yield superior PFS outcomes compared to endocrine therapy alone ( 7 - 9 ).…”