409TiPPHASE III STUDY OF PALBOCICLIB IN COMBINATION WITH EXEMESTANE VS. CAPECITABINE, IN HORMONAL RECEPTOR (HR) POSITIVE/HER2 NEGATIVE METASTATIC BREAST CANCER (MBC) PATIENTS WITH RESISTANCE TO NON-STEROIDAL AROMATASE INHIBITORS (NSAI): PEARL STUDY (GEICAM/2013-02_CECOG/BC.1.3.006)

ABSTRACT Background: Endocrine therapy (ET) is the cornerstone treatment for HR–positive, HER2-negative breast cancer (BC) patients. AIs have become the treatment of choice in postmenopausal patients. The high response rates with ET in these patients are partially undermined by the resistance developed by most of them over time. On early disease recurrence/progression to AIs, the treatment options include other AI, estrogen-receptor antagonists or chemotherapy (being capecitabine one of the best options). Preclinical data suggest that ER + /HER2- BC are dependent on cyclin-dependent kinases 4/6 (CDK4/6) function; the inhibition of this target may be effective in delaying/reverting endocrine resistance. Palbociclib is an oral novel CDK4/6 inhibitor that seems to be synergistic with ET in preclinical and clinical studies. Trial design: This is an international (6 countries) randomized phase III study. Patients are randomized 1:1 to exemestane (25 mg daily) plus palbociclib (125 mg daily x3 weeks every 4 weeks) vs. capecitabine (1,250 mg/m2 twice daily x2 weeks every 3 weeks). Postmenopausal patients with HR + /HER2 MBC are eligible if resistant to previous NSAI (letrozole or anastrozole) defined as: recurrence while on or within 12 months after the end of adjuvant treatment or progression while on or within 1 month after the end of treatment for MBC. Previous chemotherapy is permitted either in the (neo)adjuvant setting and/or as first line for MBC. Patients must have measurable disease according to RECIST 1.1 or lytic bone lesions in the absence of measurable disease. The primary objective is Progression-Free Survival (PFS); secondary objectives are overall survival, response rate, clinical benefit rate, response duration, safety, quality of life and biomarker's defined changes. The study will recruit 348 patients to detect a difference of 2.75 months in the median PFS (from 6 to 8.75 months; hazard ratio= 0.686), with a power of 80% and a 5% two sided significance level. The study started recruitment in March 2014 and 10 patients have been included so far (ClinTrials.gov reference NCT02028507). Disclosure: C.H. Bartlett: Employee of Pfizer and hold Pfizer stock; M. Koehler: Employee of Pfizer and hold Pfizer stock; C. Zielinski: Honoraria and Advisory Boards from Roche. All other authors have declared no conflicts of interest.