Abstract OT3-1-03: An open-label, multicentre, phase IIIb study with intravenous administration of pertuzumab, subcutaneous trastuzumab, and a taxane in patients with HER2-positive metastatic breast cancer (SAPPHIRE)
Authors: Woodward Natasha , De Boer Richard H , Redfern Andrew , Von Neumann-Cosel Vita , Heath Ronelle M , Beith Jane 
Published: May 2015

Abstract
Background: The primary goals of treatment for patients (pts) with metastatic breast cancer (mBC) are maximising survival and preserving the quality of life. Intravenous (IV) trastuzumab has proven clinical benefits in pts with human epidermal growth factor receptor 2 (HER2)-positive mBC. Pertuzumab also targets HER2 through an independent epitope to that of trastuzumab. Addition of pertuzumab to the established combination of trastuzumab and docetaxel has shown improved efficacy with acceptable toxicity in mBC (Swain et al. Lancet Oncol 2013;14:461-71); they are considered standard of care. Subcutaneous (SC) and IV trastuzumab formulations have shown comparable efficacy but SC administration is preferred by pts for reducing duration of clinic visits (Pivot, et al. Lancet Oncol 2013;14: 962–970). The combination of IV pertuzumab and SC trastuzumab has not been studied. The aim is to assess safety, tolerability, and efficacy of combining IV pertuzumab with SC trastuzumab and a taxane, as first-line therapy in pts with HER2-positive mBC.
Trial Design: SAPPHIRE is an open-label, multicentre, Phase IIIb study. Pts will receive IV pertuzumab every 3 weeks with a loading dose of 840 mg and subsequent doses at 420 mg combined with SC trastuzumab at 600 mg/5 mL every 3 weeks and a taxane (docetaxel, paclitaxel, or nab-paclitaxel; regimen determined by the investigator). Treatment will continue until disease progression, unacceptable toxicity, or pts withdraw consent, whichever occurs first. The study is expected to run for 42 months.
Eligibility: Pts aged ≥18 years old with histologically or cytologically confirmed HER2-positive [immunohistochemistry (IHC) positive at 3+ or in situ hybridisation-positive (ISH+)] mBC with at least one measurable lesion and/or non-measurable disease according RECIST version 1.1 and ECOG performance status (PS) 0-2 are eligible.
Specific Aims: The primary objective is to assess the safety and tolerability of combining IV pertuzumab with SC trastuzumab and investigator’s choice taxane chemotherapy. The secondary objectives are to assess the efficacy of the first-line combination of pertuzumab, trastuzumab, and taxane chemotherapy and second-line treatments for mBC after disease progression.
Statistical Methods: Primary safety analyses will report incidence and severity of adverse events (AEs)/serious AEs, AEs leading to premature discontinuation of study treatment and evidence of cardiac dysfunction. Secondary safety analyses will include exposure and duration of study treatment, ECOG PS and laboratory data. Secondary efficacy analyses will report the overall response rate, progression-free survival, event-free survival and overall survival. Continuous data will be summarised using mean, median, range, standard deviation, and standard error. Discrete data will be summarised using frequency counts and percentages. Time-to-event analyses will be based on Kaplan-Meier methodology.
Accrual: The planned 50 pts will be recruited from 13 Australian Centres. The study started in December 2013 with 24 pts now enrolled. Clinicaltrials.gov#NCT02019277.
Citation Format: Natasha Woodward, Richard H De Boer, Andrew Redfern, Vita Von Neumann-Cosel, Ronelle M Heath, Jane Beith. An open-label, multicentre, phase IIIb study with intravenous administration of pertuzumab, subcutaneous trastuzumab, and a taxane in patients with HER2-positive metastatic breast cancer (SAPPHIRE) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-1-03.