Results From the First Multicenter, Open-label, Phase IIIb Study Investigating the Combination of Pertuzumab With Subcutaneous Trastuzumab and a Taxane in Patients With HER2-positive Metastatic Breast Cancer (SAPPHIRE)

Introduction The primary objective of this study was to assess the safety and tolerability of combination pertuzumab, subcutaneous trastuzumab (Herceptin), and investigator’s choice of taxane chemotherapy in previously untreated patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. Efficacy was a secondary objective. Patients and Methods This study was an open-label, non-randomized study of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who had no previous systemic non-hormonal anti-cancer therapy for metastatic disease. The primary endpoints included adverse events (AE), serious AEs, and cardiac AEs. Secondary endpoints included overall response rate, progression-free survival, and overall survival. Patients were treated with pertuzumab and subcutaneous trastuzumab in 3-weekly cycles with taxane chemotherapy until disease progression, unacceptable toxicity, or withdrawal of consent and followed for a minimum of 24 months from initiation of study treatment. Results Fifty patients were enrolled and included in the analysis. All patients experienced at least 1 AE, with diarrhea, fatigue, peripheral neuropathy, alopecia, rash, and nausea the most common. Three patients experienced at least 1 grade 3 event of suspected cardiac origin (cardiac failure, cardiomyopathy, hypertension). Six patients withdrew from therapy owing to AEs (cardiac failure, drug hypersensitivity, decreased left ventricular ejection fraction, syncope, and bullous dermatitis). Taxane chemotherapy comprised nab-paclitaxel (74.0% of patients), docetaxel (28.0%), or paclitaxel (4.0%). The overall response rate was 73.3% (95% confidence interval, 58.1%-85.4%), the median progression-free survival was 17.0 months (95% confidence interval, 12.5-31.2 months), and the median overall survival was not reached. Conclusions Subcutaneous trastuzumab in this combination has an acceptable safety and tolerability profile, including cardiac safety profile. Safety and efficacy appear similar to previous studies of intravenous trastuzumab in this combination.