J Cancer 2017; 8(11):2004-2009. doi:10.7150/jca.18196

Research Paper

Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inhibitor Discontinuation

Sami I. Bashour1, Iman Doostan2, Khandan Keyomarsi2, Vicente Valero1, Naoto T. Ueno1, Powel H. Brown1,3, Jennifer K. Litton1, Kimberly B. Koenig1, Meghan Karuturi1, Sausan Abouharb1, Debasish Tripathy1, Stacy L. Moulder-Thompson1*, Nuhad K. Ibrahim1*✉

1. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Houston, TX 77030.
2. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.
3. Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.
*Both Co-authors contributed equally to this work

Abstract

Background: CDK 4 and 6 inhibitors (CDK4/6i), which arrest unregulated cancer cell proliferation, show clinical efficacy in breast cancer. Unexpectedly, a patient treated on a CDK4/6i-based trial, as first-line therapy in metastatic breast cancer, developed rapid disease progression following discontinuation of study drug while receiving standard second-line therapy off trial. We thus sought to expand this observation within a population of patients treated similarly at The University of Texas MD Anderson Cancer Center.

Methods: Using an IRB-approved protocol, 4 patients previously enrolled on CDK4/6i trials were analyzed for outcomes after discontinuing study drug. These patients were treated on a randomized trial of first-line endocrine therapy +/- a CDK4/6i. Rapid disease progression was defined as progression occurring within 4 months of CDK4/6i discontinuation.

Results: In total, 4 patients developed rapid disease progression and died; 2 of whom died within 6 months of CDK4/6i discontinuation.

Conclusion: This case series suggests a potential for rapid disease progression following CDK4/6i discontinuation. However, the clinical course following progression must be validated in large CDK4/6i clinical trials and standard-of-care cohorts. If confirmed, such observations may alter the algorithm for subsequent therapy in patients with disease progression on CDK4/6i. Nevertheless, the need remains to define a mechanistic basis for this rapid progression and formulate alternative therapeutic strategies.

Keywords: Breast Cancer, Estrogen Receptor-Positive Breast Cancer, Rapid Disease Progression, CDK and CDK Inhibitors

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How to cite this article:
Bashour SI, Doostan I, Keyomarsi K, Valero V, Ueno NT, Brown PH, Litton JK, Koenig KB, Karuturi M, Abouharb S, Tripathy D, Moulder-Thompson SL, Ibrahim NK. Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inhibitor Discontinuation. J Cancer 2017; 8(11):2004-2009. doi:10.7150/jca.18196. Available from http://www.jcancer.org/v08p2004.htm