Despite the high efficacy of anti-HER2 agents, HER2+ metastatic breast cancer remains incurable and in need of additional therapeutic options. Persistent activation of the cyclin D1/CDK4 axis has been identified as a mediator of resistance to anti-HER2 therapy but clinical data of the benefit of CDK4/6 inhibitors in combination with trastuzumab is lacking. PATRICIA is a Simon 2-Stage study to evaluate the efficacy of combining trastuzumab plus palbociclib, with or without letrozole, assessed by progression-free survival (PFS) in pretreated HER2-positive patients.
Postmenopausal HER2-positive patients treated with 2-4 prior systemic anticancer treatment lines that must involve trastuzumab or another anti-HER2 treatment in the metastatic setting are included in three cohorts: A: HR-negative, receiving trastuzumab and palbociclib; B1: HR-positive, receiving trastuzumab and palbociclib; B2: HR-positive, receiving trastuzumab, palbociclib and letrozole. Palbociclib is administered at 200 mg/day for 14 days of 21-day cycles. Trastuzumab and letrozole are administered at usual doses. As these combinations have not been tested in phase I trials, we incorporated a 2 cycles-safety run-in phase with the first 6 patients of each regimen. The primary objective is to assess clinical efficacy measured as PFS at 6 months (PFS6). Assuming an increase of at least 20% in PFS6 by the addition of palbociclib +/- letrozole to trastuzumab, PFS6 should be ≥ 50% for a cohort to be successful and proceed to stage 2. According to this, it will be necessary to include 15 patients in each cohort in stage 1. In stage 2, each cohort may continue recruitment for up to 46 patients. Translational research searching for predictive biomarkers will be implemented. To date, 43 patients, 13 in A and 15 in each B cohort, have been included in 14 sites across Spain. An independent safety data committee was held twice during the study. The committee recommended that study continue enrollment as planned. The first stage efficacy analysis is intended for December 2017.
Clinical trial identification
Legal entity responsible for the study
SOLTI Breast Cancer Research Group
All authors have declared no conflicts of interest.