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.
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 ≤ 3 prior chemotherapies. Patients received G (1200 mg/m2) on days 1 and 8 of a q 3 week (w) cycle, and H (8 mg/kg load → 6 mg/kg) and P (840 mg load → 420 mg) q3w. The primary endpoint is PFS at 3 months. Secondary 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.
As of April 11, 2016, 22 patients are enrolled; 17 are evaluable at 3 months and 5 have not had 3-month evaluation. At 3 months, 12/17 (71%) are progression free (1 CR, 4 PR, 7 SD); 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. 5 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.
The preliminary 3 month-PFS is 71% in evaluable patients, and updated data will be presented. These findings suggest clinical benefit when P is continued beyond progression.
Clinical trial identification
NCT02252887 September 26, 2014
Legal entity responsible for the study
Memorial Sloan Kettering Cancer Center
All authors have declared no conflicts of interest.