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

• Published in: Journal of clinical oncology Vol. 37; no. 15_suppl; p. 1053
• Main Authors: dos Anjos, Carlos Henrique, Razavi, Pedram, Herbert, Joshua, Colon, Jodecy, Gill, Kaitlyn, Modi, Shanu, Bromberg, Jacqueline, Dang, Chau T., Liu, Dazhi, Norton, Larry, Chandarlapaty, Sarat, Robson, Mark E., Jhaveri, Komal L.
• Format: Journal Article
• Language: English
• Published: 20.05.2019
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2019.37.15_suppl.1053

Abstract only 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.