Phase II study of gemcitabine, trastuzumab, and pertuzumab for HER2-positive metastatic breast cancer after prior pertuzumab-based therapy

Abstract

Background: The combination of taxanes with trastuzumab (H) and pertuzumab (P) for first line treatment of HER2‐positive metastatic breast cancer (MBC) is associated with improved progression‐free survival (PFS) and overall survival (OS). Treatment per physician's choice with anti‐HER2 therapy after second line therapy is associated with a median PFS of 3 months. While continued use of H in therapeutic combinations after progression on H‐based therapy is common, the efficacy of continuing HP‐based treatment after progression on P‐based therapy is unknown. Methods: This is a single arm phase II trial of gemcitabine (G) with HP. Eligible patients had HER2‐ positive (IHC 3+ or FISH >= 2.0) MBC with prior HP‐based treatment and 6 mg/kg) and P (840 mg load ‐> 420 mg) q3w. The primary endpoint is PFS at 3 months. Secondary 2 endpoints include OS, safety and tolerability. An exploratory endpoint is to compare PFS by RECIST criteria versus 18‐F FDG‐PET response criteria. Using a Simon optimal 2‐stage design, 21 patients were enrolled in stage 1. The successful 3‐month PFS rate for stage 1 was set at 57% to allow accrual to stage 2 for a total of 45 patients. The study therapy will be considered successful if at least 27/45 (60%) patients are progression free at 3 months. Results: As of June 9, 2016, 28 patients are enrolled; 21 are evaluable at 3 months and 7 have not had 3‐month evaluation. At 3 months, 16/21 (76%) are progression free; 5 patients have progressed. The 3 month‐PFS results for evaluable patients will be updated. There are no cardiac or febrile neutropenic events to date. Initially, 5 of 22 (23%) patients required G dose reduction (4 due to grade 3 neutropenia and 1 due to grade 3 vomiting) and the study was amended to lower initial G dose to 1000 mg/m2 . Conclusions: The preliminary 3 month‐PFS is 76% (95% CI 55% to 89%) in evaluable patients, and updated data will be presented. These findings suggest clinical benefit when P is continued beyond progression.