Background:
CDK4/6 inhibition (CDK4/6i) has a significant role in contemporary management of hormone receptor positive/HER2 negative (HR+/HER2-) metastatic breast cancer (MBC). The addition of a CDK4/6i to endocrine therapy (ET) in HR+/HER2- MBC leads to prolongation of progression-free survival in previously untreated and pre-treated HR+/HER2- MBC. Mechanisms of resistance to CDK4/6i are not well described, and it is not known if continuation of CDK4/6i with subsequent lines of ET improves outcomes over ET alone. Further, preclinical data suggest combination therapy with ET, CDK4/6i, and anti-PDL1 may provide synergistic efficacy. The PACE trial was designed to determine the optimal subsequent line of therapy in patients (pts) with HR+ /HER2- MBC that has progressed despite prior CDK4/6 inhibition and endocrine therapy.
Methods:
PACE (NCT03147287) is a multicenter phase II trial randomizing pts 1:2:1 to Arm A: fulvestrant alone (with option for Palbociclib (P) monotherapy crossover at time of progression); Arm B: fulvestrant + P; or Arm C: fulvestrant + P + avelumab. The primary objective is to evaluate progression-free survival (PFS) with the combination of fulvestrant + P vs. fulvestrant alone; secondary objectives include overall response (OR), safety and tolerability, and PFS comparisons of avelumab containing arm vs other arms. Exploratory objectives include assessment of outcomes in predefined molecular subgroups (i.e. ESR mutation, PI3K mutation, and loss of Rb); and comparing OR by RECIST vs irRECIST in the avelumab cohort. Extensive molecular profiling of tissue, ctDNA, and CTCs for markers of response and resistance to therapy is also planned. Eligible pts have HR+/HER2- MBC, with prior response to and subsequent progression on any CDK4/6i and ET, defined as at least 6 months of prior treatment, with confirmed subsequent progression, and no more than one prior P dose reduction for toxicity. Pts may have had 1-2 prior ET (aromatase inhibitor or tamoxifen), and 0-1 prior lines of chemotherapy. A sample size of 220 patients is planned.
Citation Format: Mayer EL, Wander SA, Regan MM, DeMichele AM, Forero A, Rimawi MF, Ma CX, Cristofanilli M, Anders CK, Huang Bartlett C, Koehler M, Winer EP, Burstein HJ. Palbociclib after CDK inhibitor and endocrine therapy (PACE): A randomized phase II study of fulvestrant versus palbociclib plus fulvestrant, with and without avelumab, for CDK inhibitor pre-treated HR+/HER2- metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-05-11.
