Abstract P4-14-12: Interim results from the first open-label, multicenter, phase IIIb study investigating the combination of pertuzumab with subcutaneous trastuzumab and a taxane in patients with HER2-positive metastatic breast cancer (SAPPHIRE)
Authors: Woodward N , De Boer RH , Redfern A , White M , Young J , Truman M , Beith J 
Published: May 2016

Abstract
Background: Intravenous (IV) trastuzumab has proven clinical benefits in patients (pts) with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). The use of pertuzumab, which targets HER2 through an independent epitope to that of trastuzumab, in combination with IV trastuzumab and docetaxel has shown improved efficacy with acceptable toxicity in metastatic (m) BC. Subcutaneous (SC) and IV trastuzumab formulations have shown comparable efficacy. This study aimed to assess the safety, tolerability, and efficacy of combining IV pertuzumab with SC trastuzumab and a taxane, as 1st-line therapy in pts with HER2+ mBC, a combination for which results have not previously been reported. Here we present demographics and interim safety data.
Methods: This is an open-label, multicentre, phase IIIb study. The primary objective was the safety and tolerability of IV pertuzumab with SC trastuzumab and investigator's choice of taxane. Pts aged ≥18 years with confirmed HER2-positive [IHC3+ or ISH+] mBC with at least one measurable lesion and/or non-measurable disease according to RECIST version 1.1 and ECOG performance status (PS) 0-2 were included. Pts received IV pertuzumab every 3 weeks (loading dose=840 mg; subsequent doses=420mg) combined with SC trastuzumab at 600mg/5mL every 3 weeks and the investigator's choice of taxane (docetaxel, paclitaxel, or nab-paclitaxel). Treatment continued until disease progression, unacceptable toxicity, or consent was withdrawn, whichever occurred first. The incidence and severity of adverse events (AEs), serious (S) AEs and AEs leading to premature discontinuation of study treatment were analyzed.
Results: The planned 50 pts have been recruited from 12 centres; mean age 53 (SD-12.0) years; the majority white (84%), ECOG PS 0 (n=33) and PS 1 (n=15). 98% were females; 61% post-menopausal. Taxanes of choice were nab-paclitaxel (n=36), docetaxel (n=13) and paclitaxel (n=1). Any grade AEs (n=627) were reported in 100% pts; majority grade 1-2, the most common being diarrhoea, fatigue, peripheral neuropathy, alopecia, nausea, rash, headache and vomiting. Grade 3+ AEs (n=54) were reported in 52% pts, most commonly neutropenia (10%), febrile neutropenia (8%) and diarrhoea (6%). SAEs (n=36) were reported in 48% pts; most commonly pyrexia (14%), febrile neutropenia (8%), neutropenia (4%), pulmonary embolism (4%) and cellulitis (4%). Five AEs of suspected cardiac disorders were reported in 4 pts (atrial fibrillation, cardiomyopathy, myocardial ischemia, palpitations and ejection fraction decreased). AEs leading to study drug discontinuation (n=3) were reported in 3 pts (LVEF decreased, syncope and blister). AEs leading to chemotherapy discontinuation (n=14) were reported in 20% pts.
Conclusion: We report the first data on the use of pertuzumab with SC trastuzumab. The observed safety profile is consistent with that previously reported in the CLEOPATRA (Baselga, et al. NEJM 2012;366:109-19), PERUSE [Bachelot, et al. JCO 2014;32:5s(abstr#548)] and HannaH (Ismael, et al. Lancet Oncol 2012;13:869-78) studies, with no unexpected safety signals. Clinical trial information:NCT02019277.
Citation Format: Woodward N, De Boer RH, Redfern A, White M, Young J, Truman M, Beith J. Interim results from the first open-label, multicenter, phase IIIb study investigating the combination of pertuzumab with subcutaneous trastuzumab and a taxane in patients with HER2-positive metastatic breast cancer (SAPPHIRE). [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 P4-14-12.