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.

• Authors: Kevin Kalinsky, Melissa K Accordino, Codruta Chiuzan, Prabhjot S Mundi, Elizabeth Sakach, Claire Sathe, Heejoon Ahn, Meghna S Trivedi, Yelena Novik, Amy Tiersten, George Raptis, Lea N Baer, Sun Y Oh, Amelia B Zelnak, Kari B Wisinski, Eleni Andreopoulou, William J Gradishar, Erica Stringer-Reasor, Sonya A Reid, Anne O'Dea, Ruth O'Regan, Katherine D Crew, Dawn L Hershman
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 41 Issue 24 Pg. 4004-4013 (08 20 2023) ISSN: 1527-7755 [Electronic] United States
• PMID: 37207300 (Publication Type: Clinical Trial, Phase II, Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ERBB2 protein, human
• ribociclib
• Cyclin-Dependent Kinase 4
• Receptor, ErbB-2
• Cyclin-Dependent Kinase 6

Topics

• Humans
• Female
• Breast Neoplasms (pathology)
• Cyclin-Dependent Kinase 4
• Prospective Studies
• Receptor, ErbB-2 (metabolism)
• Double-Blind Method
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Cyclin-Dependent Kinase 6