Abstract A210: Evaluation and comparison of the CDK 4/6 inhibitor palbociclib in a panel of PDX models representing hormone-positive and -negative breast cancer

Abstract

Abstract Background: Palbociclib is a CDK 4/6 inhibitor approved in combination with letrozole in hormone-positive breast cancer. The START PDX platform comprises over 1300 fully annotated models, including a breast cancer panel of over 100 models representing each disease subtype: ~35 ER+, 20 HER2+, and 45 TNBC models. To better understand activity of CDK 4/6 inhibitors in breast cancer we screened our breast panel with single-agent palbociclib. The goal of this study was to determine and compare efficacy of a CDK 4/6 inhibitor in models representative of relevant subtypes of human breast cancer. Methods: START-PDX models were established from tissue biopsies or tissue samples taken from breast cancer patients. Sensitivity of 100 breast tumor models to single-agent palbociclib administered orally once daily at 75 mg/kg for a minimum of twenty-eight days was evaluated in a coclinical screen format. Study endpoints included mean tumor volume and time from treatment initiation with %T/C values and tumor regression reported at study completion. Results: ER+ models showed variable sensitivity to palbociclib treatment, including ST897, ST986, and ST313, which reported tumor regressions. Interestingly, two ER+ harboring an ESR1 mutation and developed in the presence (ST941 and ST2177) or absence (ST941/HI and ST2177/HI) of exogenous estradiol reported differential sensitivity with the hormone-independent (HI) models more sensitive. Several TNBC models including ST319 and ST1394 reported sensitivity to palbociclib with %T/C values of 20% and 25%, respectively. Conclusion: We screened a panel of breast PDX models with the CDK 4/6 inhibitor palbociclib and identified activity in all breast cancer subtypes. In addition, we found a differential response in ER+, ESR1-mutant models developed in the presence and absence of exogenous estradiol. Exploration of biomarkers of sensitivity is ongoing. Citation Format: Alyssa Moriarty, Amanda Mangold, Ileana Munoz, Megan Groves, Marcus Guerra, Melissa Rundle, Kyriakos P. Papadopoulos, Drew Rasco, Anthony W. Tolcher, Amita Patnaik, Michael J. Wick. Evaluation and comparison of the CDK 4/6 inhibitor palbociclib in a panel of PDX models representing hormone-positive and -negative breast cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A210.