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

• DOI: 10.6004/jnccn.2020.7662
• Publication Date: 2021-10-13T23:18:46Z
• Authors: Seth A. Wander; Hyo S. Han; Mark L. Zangardi; Andrzej Niemierko; Veronica Mariotti; Leslie S.L. Kim; Jing Xi; Apurva Pandey; Siobhan Dunne; Azadeh Nasrazadani; Avinash Kambadakone; Casey Stein; Maxwell R. Lloyd; Megan Yuen; Laura M. Spring; Dejan Juric; Irene Kuter; Ioannis Sanidas; Beverly Moy; Therese Mulvey; Neelima Vidula; Nicholas J. Dyson; Leif W. Ellisen; Steven Isakoff; Nikhil Wagle; Adam Brufsky; Kevin Kalinsky; Cynthia X. Ma; Joyce O’Shaughnessy; Aditya Bardia
• Keywords: Palbociclib; Fulvestrant

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