Predictors of Response to CDK4/6i Retrial After Prior CDK4/6i Failure in ER+ Metastatic Breast Cancer

Mai, Nicholas, Dos Anjos, Carlos H, Razavi, Pedram, Safonov, Anton, Patil, Sujata, Chen, Yuan, Drago, Joshua Z, Modi, Shanu, Bromberg, Jacqueline F, Dang, Chau T, Liu, Dazhi, Norton, Larry, Robson, Mark, Chandarlapaty, Sarat, Jhaveri, Komal (May 2024) Predictors of Response to CDK4/6i Retrial After Prior CDK4/6i Failure in ER+ Metastatic Breast Cancer. Res Sq.

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Abstract

After disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution. Among patients who had stopped a CDK4/6i due to toxicity, CDK4/6i retrial either immediately after with a different CDK4/6i or in a further treatment line with the same initial CDK4/6i was both safe and effective, with a median time to treatment failure (TTF) of 10.1 months (95%CI, 4.8-16.9). For patients whose disease progressed on a prior CDK4/6i, we demonstrated comparable median TTFs for patients rechallenged with the same CDK4/6i (4.3 months, 95%CI 3.2-5.5) and with a different CDK4/6i (4.7 months, 95%CI 3.7-6.0) when compared to the recent PACE, PALMIRA, and MAINTAIN trials. Exploratory genomic analysis suggested that the presence of mutations known to confer CDK4/6i resistance, such as TP53 mutations, CDK4 amplifications, and RB1 or FAT1 loss of function mutations may be molecular biomarkers predictive of CDK4/6i retrial failure.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > breast cancer diseases & disorders > cancer > cancer types
CSHL Authors:	Norton, Larry
Communities:	CSHL labs > Wigler lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2 May 2024
Date Deposited:	28 May 2024 13:14
Last Modified:	28 May 2024 13:14
PMCID:	PMC11092820
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41566

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