A large retrospective analysis of CDK 4/6 inhibitor retreatment in ER+ metastatic breast cancer (MBC).

Abstract

1053 Background: Sequential retreatment with endocrine therapy (ET) has been the clinical paradigm for ER+ MBC due to persistent dependence on hormone signaling. Recently CDK4/6i + ET have improved PFS and are routinely utilized in the first/second- line setting. Whether this paradigm of sequential retreatment holds for CDK 4/6i is unknown. To evaluate the potential benefit of CDK4/6i re-treatment we conducted this retrospective analysis. Methods: We identified ER+/HER2- MBC pts treated with ≥ 2 lines of CDK4/6i at our institution between 2015-2018. We categorized pts based on reason for discontinuation of their first CDK4/6i: cohort 1 – switch to alternate CDK4/6i due to toxicity; cohort 2 – retreatment with same CDK4/6i beyond progression with change of ET and cohort 3- switch to alternate CDK4/6i as monotherapy or with same or another ET. We analyzed pt demographics, imaging reports and time to subsequent therapy (TTST) for every CDK4/6i line for each cohort. If a pt received > 2 lines of CDK4/6i, then that pt was evaluated for every CDK4/6i exposure. Results: 135 pts received ≥ 2 lines of CDK4/6i treatment (Tx). Cohorts 1, 2 and 3 had 23, 43 pts and 84 pts respectively. In Cohort 2, 95% of pts received 2 subsequent CDK 4/6i + ET Tx; 56% had the second CDK4/6i in second-line met setting. TTST1 (1st CDK4/6i Tx) was 9.6m (95% CI 4.9 - 11 m), TTST2 (second CDK4/6i Tx) was 4.5m (95% CI 3.3 – 7.6 m) and 35% had TTST2 ≥ 24 weeks. For Cohort 3, 48% were retreated with a different CDK 4/6i in ≥ fifth-line. 51% received 2 subsequent CDK 4/6i Tx with 18% in second-line met setting. TTST1 was 9.6 m (95% CI 5.9 – 12 m), TTST2 was 4.4 m (95% CI 3.8 – 5.9 m) and 29% had TTST2 ≥ 24 weeks. In cohort 3, 29% (n=24) pts had PD as best response at the time of first CDK4/6i exposure but 29% (7/24) achieved a radiologic response to their second CDK4/6i Tx. Pts had tumor sequencing using MSK-IMPACT which will be correlated with TTST. Conclusions: This large single institution retrospective analysis suggests that retreatment with a CDK4/6i regimen should be evaluated in prospective trials. Additionally, despite PD as best response with the first CDK4/6i (palbociclib/ribociclib) regimen, a subset of pts had radiologic response to a subsequent abemaciclib-containing regimen, which is an hypothesis generating observation.