Abstract 1747
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 (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 standard, 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 (pts) had HER2-positive (IHC 3+ or FISH ≥ 2.0) MBC with prior HP-based treatment and ≤ 3 prior chemotherapies. Pts 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. The study therapy will be considered successful if at least 27/45 (60%) patients are progression free at 3 months.
Results
As of 27 April 2017, 45 of 45 pts are enrolled; 39 are evaluable at 3 months and 6 have not had 3-month evaluation. At 3 months, 30/39 (77%) are progression free (1 CR, 8 PR, 21 SD); 9 pts progressed. There are no cardiac or febrile neutropenic events to date. 4 pts required G dose reduction (3 grade 3 neutropenia and 1 grade 3 vomiting) and the study was amended to lower initial G dose to 1000 mg/m2.
Conclusions
The preliminary 3 month-PFS is 77% in evaluable pts (95% CI 62% to 87%). The updated 3 month-PFS results will be presented. Continuation of P beyond progression is associated with apparent clinical benefit. A randomized trial is justified to confirm this clinically important observation.
Clinical trial identification
NCT02252887
Legal entity responsible for the study
Memorial Sloan Kettering Cancer Center
Funding
Genentech/Roche
Disclosure
All authors have declared no conflicts of interest.