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

Dr. Anjan Patel's Thoughts

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

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.

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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