Clinical Outcomes With Abemaciclib After Prior CDK4/6 Inhibitor Progression in Breast Cancer: A Multicenter Experience

Authors:
Seth A. Wander Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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 MD, PhD
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Hyo S. Han Moffitt Cancer Center, Tampa, Florida;

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Mark L. Zangardi Massachusetts General Hospital Cancer Center, and

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Andrzej Niemierko Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Veronica Mariotti Moffitt Cancer Center, Tampa, Florida;

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Leslie S.L. Kim Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, Texas;

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Jing Xi Washington University, St. Louis, Missouri;

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Apurva Pandey University of Pittsburgh, Pittsburgh, Pennsylvania;

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Siobhan Dunne Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, Texas;

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Azadeh Nasrazadani University of Pittsburgh, Pittsburgh, Pennsylvania;

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Avinash Kambadakone Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Casey Stein Massachusetts General Hospital Cancer Center, and

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Maxwell R. Lloyd Massachusetts General Hospital Cancer Center, and

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Megan Yuen Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Laura M. Spring Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Dejan Juric Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Irene Kuter Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Ioannis Sanidas Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Beverly Moy Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Therese Mulvey Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Neelima Vidula Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Nicholas J. Dyson Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Leif W. Ellisen Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Steven Isakoff Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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Nikhil Wagle Harvard Medical School, Boston, Massachusetts;
Dana-Farber Cancer Institute, and
Broad Institute of MIT and Harvard, Boston, Massachusetts; and

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Adam Brufsky University of Pittsburgh, Pittsburgh, Pennsylvania;

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Kevin Kalinsky Columbia University Irving Medical Center, New York, New York.

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Cynthia X. Ma Washington University, St. Louis, Missouri;

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Joyce O’Shaughnessy Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, Texas;

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Aditya Bardia Massachusetts General Hospital Cancer Center, and
Harvard Medical School, Boston, Massachusetts;

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 MD, MPH
Volume/Issue:
Volume 19: Issue 13
Online Publication Date:
24 Mar 2021
DOI:
https://doi.org/10.6004/jnccn.2020.7662
Restricted access

Background: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are widely used as first-line therapy for hormone receptor–positive metastatic breast cancer (HR+ MBC). Although abemaciclib monotherapy is also FDA-approved for treatment of disease progression on endocrine therapy, there is limited insight into the clinical activity of abemaciclib after progression on prior CDK4/6i. Patients and Methods: We identified patients with HR+ MBC from 6 cancer centers in the United States who received abemaciclib after disease progression on prior CDK4/6i, and abstracted clinical features, outcomes, toxicity, and predictive biomarkers. Results: In the multicenter cohort, abemaciclib was well tolerated after a prior course of CDK4/6i (palbociclib)-based therapy; a minority of patients discontinued abemaciclib because of toxicity without progression (9.2%). After progression on palbociclib, most patients (71.3%) received nonsequential therapy with abemaciclib (with ≥1 intervening non-CDK4/6i regimens), with most receiving abemaciclib with an antiestrogen agent (fulvestrant, 47.1%; aromatase inhibitor, 27.6%), and the remainder receiving abemaciclib monotherapy (19.5%). Median progression-free survival for abemaciclib in this population was 5.3 months and median overall survival was 17.2 months, notably similar to results obtained in the MONARCH-1 study of abemaciclib monotherapy in heavily pretreated HR+/HER2-negative CDK4/6i-naïve patients. A total of 36.8% of patients received abemaciclib for ≥6 months. There was no relationship between the duration of clinical benefit while on palbociclib and the subsequent duration of treatment with abemaciclib. RB1, ERBB2, and CCNE1 alterations were noted among patients with rapid progression on abemaciclib. Conclusions: A subset of patients with HR+ MBC continue to derive clinical benefit from abemaciclib after progression on prior palbociclib. These results highlight the need for future studies to confirm molecular predictors of cross-resistance to CDK4/6i therapy and to better characterize the utility of abemaciclib after disease progression on prior CDK4/6i.

Submitted May 18, 2020; accepted for publication September 28, 2020.

Author contributions: Study concept and design: Wander, Han, Brufsky, Kalinsky, Ma, O’Shaughnessy, Bardia. Data acquisition and provision of study materials: All authors. Initial manuscript draft: Wander, Han, Zangardi, Niemierko, Brufsky, Kalinsky, Ma, O’Shaughnessy, Bardia. Critical feedback and development of final manuscript: All authors.

Disclosures: Dr. Wander has reported serving as a consultant for Foundation Medicine, Veracyte, Eli Lilly, and Puma Biotechnology. Dr. Han has reported receiving grant/research support from Arvinas, AbbVie, Bristol-Myers Squibb, Daiichi Pharma, G1 therapeutics, GlaxoSmithKline, Horizon, Karyopharm, Marker Therapeutics, Novartis, Pfizer, Prescient, Seattle Genetics, and Zymeworks, and serving on the speakers’ bureau of Eli Lilly. Dr. Kambadakone has reported receiving grant/research support from Philips Healthcare and GE Healthcare. Dr. Moy has reported receiving grant/research support from Puma Biotechnology. Dr. Spring has reported serving as a consultant/advisory board member for Novartis, Lumicell, Puma Biotechnology; receiving travel fees from Merck and Tesaro; and receiving grant/research support from Merck and Tesaro. Dr. Vidula has reported receiving grant/research support from Radius, Daehwa, Merck, Pfizer, and Novartis, and serving on the advisory board of AbbVie. Dr. Wagle has reported serving as a consultant and being a former stockholder of Foundation Medicine; serving as a consultant and receiving grant/research support from Novartis; receiving research support from PUMA biotechnology; serving on the advisory board for Section 32; serving on the advisory board and being a stockholder for Relay Therapeutics; and serving as a consultant for Eli Lilly. Dr. Brufsy has reported serving as a scientific advisor for Pfizer and Eli Lilly. Dr. Kalinsky has reported having a spouse who is an employee at Pfizer; holding stock in Array BioPharma; serving as an advisor/consultant for Biotheranostics, Eli Lilly, Pfizer, Novartis, Eisai, AstraZeneca, Merck, Seattle Genetics, and Cyclacel; serving on the speakers’ bureau for Eli Lilly; and receiving grant/research support from Incyte, Genentech, Eli Lilly, Pfizer, Calithera Biosciences, Acetylon, Seattle Genetics, Amgen, Zeno Pharmaceuticals, and CytomX Therapeutics. Dr. Ma has reported receiving grant/research support from Pfizer and Puma Biotechnology, and receiving consulting fees from AstraZeneca, Seattle Genetics, Agendia, Eli Lilly, Novartis, Tempus, and Pfizer. Dr. O’Shaughnessy has reported receiving honoraria and consulting fees from AbbVie Inc., Agendia, AstraZeneca, Bristol-Myers Squibb, Celgene Corporation, Eisai, Genentech, Genomic Health, GRAIL, Immunomedics, Heron Therapeutics, Ipsen Biopharmaceuticals, Jounce Therapeutics, Eli Lilly, Merck, Myriad, Novartis, Ondonate Therapeutics, Pfizer, Puma Biotechnology, Prime Oncology, Roche, Seattle Genetics, and Syndax Pharmaceuticals. Dr. Bardia has disclosed serving as a consultant/advisory board member for Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Taiho, Sanofi, Diiachi Pharma/AstraZeneca, Puma, Biothernostics Inc., Phillips, Eli Lilly, and Foundation Medicine, and receiving grant/research support from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, and Diiachi Pharma/Astra Zeneca. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Aditya Bardia, MD, MPH, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA 02114-2696. Email: bardia.aditya@mgh.harvard.edu

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Print ISSN:
1540-1405
Online ISSN:
1540-1413
Publisher:
National Comprehensive Cancer Network
Cover Journal of the National Comprehensive Cancer Network
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Copyright:
Copyright © 2021 by the National Comprehensive Cancer Network 2021
Page Numbers:
8
Article Category:
Research Article
Received:
18 May 2020
Accepted:
28 Sep 2020
Print Publication Date:
01 Dec 2021
Online Publication Date:
24 Mar 2021

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