Abstract P6-18-39: Abemaciclib after prior palbociclib exposure in patients with metastatic hormone-receptor positive (HR+)/HER2- breast cancer
Authors: Wander SA , Spring LM , Stein CR , Yuen M , Zangardi M , O'Shaughnessy J , Bardia A 
Published: May 2019

Introduction: The advent of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) has transformed the clinical practice of HR+/HER2- metastatic breast cancer. Palbociclib, ribociclib, and abemaciclib have been approved in conjunction with anti-estrogens, while abemaciclib has also been approved as monotherapy based on single agent activity in the MONARCH-1 trial (objective response rate/ORR: 19.7% and median progression-free-survival/PFS = 6.0 months; Dickler M et al CCR 2017). However, there is limited insight into the mechanisms governing resistance to CDK 4/6i and the potential utility of continued CDK4/6i after progression on a prior CDK 4/6i-based therapy.

Methods: We evaluated the clinical outcomes of patients with metastatic HR+/HER2- breast cancer who had received abemaciclib following an initial course of palbociclib-based therapy at our institution. In addition, we conducted genomic analysis utilizing next-generation sequencing of tissue samples and blood (cell-free DNA/cfDNA analysis) where available.

Results: From June, 2014 through July, 2018, a total of 49 patients received abemaciclib, and 14 patients had prior palbociclib exposure. One patient was deceased shortly after initiating abemaciclib and one patient was lost to follow-up. Among the 12 remaining patients, eight had sequential courses of CDK4/6-based therapy, while four patients had at least one intervening non-CDK 4/6i based regimen. At data-cutoff of 8/15/2018, five patients (41.7%) had early progression on abemaciclib (PFS equal to or less than 120 days) while three (25%) patients had ongoing benefit (PFS greater than 120 days, two of three actively on therapy). Three additional patients had recently initiated abemaciclib therapy (less than 120 days prior to current analysis). Preliminary analysis of baseline cfDNA results in patients with early progression on abemaciclib therapy after prior CDK4/6i revealed the presence of RB1 mutation, FGFR1 amplification, and TP53 mutation, among others. Additional analyses with mature clinical data (including updated PFS and ORR), toxicity assessment during secondary CDK4/6i exposure, and further analysis of genomic sequencing results will be provided at the meeting.

Conclusions: The majority of patients had early disease progression on abemaciclib after prior exposure to CDK4/6i suggesting potential cross-resistance to CDK4/6i mediated by common drivers. However, a subset of patients derived clinical benefit with continued exposure to CDK4/6i, highlighting the need for additional research to evaluate potential predictive biomarkers and guide rational utilization of continued CDK4/6 blockade in metastatic HR+/HER2- breast cancer.

Citation Format: Wander SA, Spring LM, Stein CR, Yuen M, Zangardi M, O'Shaughnessy J, Bardia A. Abemaciclib after prior palbociclib exposure in patients with metastatic hormone-receptor positive (HR+)/HER2- breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-39.