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

Author(s): Kevin Kalinsky, MD, MS1; Melissa K. Accordino, MD, MS2; Codruta Chiuzan, PhD3; Prabhjot S. Mundi, MD2; Elizabeth Sakach, MD1; Claire Sathe, MD2; Heejoon Ahn, MS3; Meghna S. Trivedi, MD, MS2; Yelena Novik, MD4; Amy Tiersten, MD5; George Raptis, MD6; Lea N. Baer, MD7; Sun Y. Oh, MD8; Amelia B. Zelnak, MD9; Kari B. Wisinski, MD10; Eleni Andreopoulou, MD11; William J. Gradishar, MD12; Erica Stringer-Reasor, MD13; Sonya A. Reid, MD14; Anne O’Dea, MD15; Ruth O’Regan, MD16; Katherine D. Crew, MD, MS2; and Dawn L. Hershman, MD, MS2
Source: DOI: 10.1200/JCO.22.02392 Journal of Clinical Oncology
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Interesting approach where endocrine therapy was changed after progression on 1L therapy and the ribociclib was continued.


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.


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%.


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.


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.

Author Affiliations

1Winship Cancer Institute, Emory University, Atlanta, GA2Columbia University Irving Medical Center, New York, NY3Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, New York, NY4New York University Perlmutter Cancer Center, NYU Langone Health, New York, NY5Icahn School of Medicine at Mount Sinai, New York, NY6Zucker School of Medicine—Northwell Cancer Institute, Lake Success NY7State University of New York at Stony Brook, Stony Brook, NY8Montefiore Medical Center, Bronx, NY9Northside Hospital, Atlanta, GA10University of Wisconsin Carbone Cancer Center, Madison, WI11Weill Cornell Medicine, New York, NY12Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL13University of Alabama, Birmingham, Birmingham, AL14Vanderbilt University Medical Center, Nashville, TN15University of Kansas Medical Center, Westwood, KS16University of Rochester Medical Center, Rochester, NY

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