 MAINTAIN (NCT02632045): Study of Efficacy of Ribociclib After Progression on CDK4/6 Inhibition in Patients With HR+ HER2- Advanced Breast Cancer (A randoMized phAse II trIal of fulvestraNt wiTh or Without Ribociclib After Progression on AntI-estrogeN Therapy Plus Cyclin-dependent Kinase 4/6 Inhibition in Patients With Unresectable or Metastatic Hormone Receptor +, HER2 - Breast Cancer)  
 
J Clin Oncol. 2023 May 19. IF: 50.717 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. Kalinsky K, Accordino MK, Chiuzan C, Mundi PS, Sakach E, Sathe C, Ahn H, Trivedi MS, Novik Y, Tiersten A, Raptis G, Baer LN, Oh SY, Zelnak AB, Wisinski KB, Andreopoulou E, Gradishar WJ, Stringer-Reasor E, Reid SA, O'Dea A, O'Regan R, Crew KD, Hershman DL. Winship Cancer Institute, Emory University, Atlanta, GA; Columbia University Irving Medical Center, New York, NY; Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, New York, NY; New York University Perlmutter Cancer Center, NYU Langone Health, New York, NY; Icahn School of Medicine at Mount Sinai, New York, NY; Zucker School of Medicine-Northwell Cancer Institute, Lake Success NY; State University of New York at Stony Brook, Stony Brook, NY; Montefiore Medical Center, Bronx, NY; Northside Hospital, Atlanta, GA; University of Wisconsin Carbone Cancer Center, Madison, WI; Weill Cornell Medicine, New York, NY; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; University of Alabama, Birmingham, Birmingham, AL; Vanderbilt University Medical Center, Nashville, TN; University of Kansas Medical Center, Westwood, KS; University of Rochester Medical Center, Rochester, NY. 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. KEY OBJECTIVE; In this randomized, phase II, double-blind placebo-controlled, investigator-initiated trial, the primary objective was to determine whether there was a progression-free survival (PFS) benefit to switching endocrine therapy (ET; fulvestrant or exemestane) combined with the cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) ribociclib versus switching ET combined with placebo in patients with hormone receptor--positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) that progressed during previous ET and CDK4/6i. KNOWLEDGE GENERATED: Among patients with HR+, HER2- MBC whose tumor progressed on previous ET and CDK4/6i, there was a statistically significant improvement when switching ET and continuing a CDK4/6i with ribociclib versus switching ET and placebo in this randomized trial. Of the 119 randomly assigned participants, the majority of patients (103, 86.5%) previously received palbociclib. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, versus 23.9% and 7.4% with placebo. RELEVANCE: The introduction of any new therapy brings a question of what to do at the time of progression. The MAINTAIN trial informs treatment decisions for patients progressing on initial hormone therapy with palbociclib. Additional studies are needed to compare this approach with other second-line hormone therapy options such as phosphatidylinositol 3-kinase- and mammalian target of rapamycin-inhibitor based treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT02632045 PMID: 37207300 DOI: 10.1200/JCO.22.02392 |
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