Abstract OT3-01-09: Phase II study of gemcitabine, trastuzumab, and pertuzumab in the treatment of metastatic HER2-positive breast cancer after prior trastuzumab/pertuzumab- or pertuzumab-based therapy
Authors: Iyengar NM , Argolo D , Smyth L , Chen MF , Hudis CA , Dang CT 
Published: May 2016

Abstract
Background: Despite significant therapeutic advances in the treatment of breast cancers that overexpress human epidermal growth factor receptor-2 (HER2), the large majority of patients (pts) with metastatic disease will experience progression. The development of new HER2 directed therapies has led to improvements in progression free and overall survival; however optimal therapeutic sequencing remains under study. The combination of taxanes with trastuzumab (H) and pertuzumab (P) is active in the first line setting; however the efficacy of continuing dual anti-HER2 therapy with HP after initial progression is unknown.
Trial design: This is a single arm phase II trial of gemcitabine (G) with HP for pts with metastatic HER2-positive breast cancer who have had prior HP-based treatment. G is administered at 1200 mg/m2 on days 1 and 8 of an every 3 week cycle. H is given 8 mg/kg load → 6 mg/kg every 3 weeks or 4 mg/kg load → 2 mg/kg every week. P is given 840 mg load → 420 mg every 3 weeks. All agents will be given intravenously. This trial is currently enrolling pts.
Eligibility criteria: Eligible pts are adults with stage IV HER2-positive (3+ IHC or FISH ≥ 2.0 of primary or metastatic site) breast cancer. Pts may have received prior treatment with HP- or P-based therapy in the (neo)adjuvant, unresectable, locally advanced, or metastatic setting. In the metastatic setting, ≤ 3 prior chemotherapies are permitted. Prior G is allowed only if it was not combined with P. Bone-only non-measurable disease is permitted. Adequate organ and bone marrow function, left ventricular ejection fraction &gt; 50%, and ECOG status ≤ 1 are required. Pts with previously treated brain metastases stable for ≥ 2 months may be enrolled.
Specific aims: The primary objective is to determine the progression free survival (PFS) at 3 months. Secondary objectives include overall survival, safety and tolerability. An exploratory endpoint is to compare PFS determined by RECIST criteria versus 18-F FDG-PET response criteria.
Statistical methods: Based on historical data, the anticipated median PFS in this setting is 3 months. The study will be considered positive if the 3-month PFS is ≥ 70%. A Simon optimal 2-stage design will be used. If 12/21 pts in stage 1 are alive and progression free at 3 months, stage 2 will accrue for a total of 45 pts. If at least 27/45 pts are alive and progression free, the trial will be deemed a success. This design assumes a 10% type I and type II error.
Present accrual and target accrual: 3 out of a planned 45 pts have been enrolled.
Contact information: For more information, please visit clinicaltrials.gov (NCT02252887).
Citation Format: Iyengar NM, Argolo D, Smyth L, Chen MF, Hudis CA, Dang CT. Phase II study of gemcitabine, trastuzumab, and pertuzumab in the treatment of metastatic HER2-positive breast cancer after prior trastuzumab/pertuzumab- or pertuzumab-based therapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-01-09.