Abstract P4-21-31: Updated safety 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)
Authors: Woodward N , De Boer RH , Redfern A , White M , Roberts W , Truman M , Beith J 
Published: March 2017

Abstract
Background: Pertuzumab targets the human epidermal growth factor receptor 2 (HER2) through an independent epitope to that of trastuzumab. Improved efficacy with acceptable toxicity has been shown, in metastatic breast cancer (mBC) for pertuzumab in combination with intravenous (IV) trastuzumab and docetaxel.1 This study aimed to assess the safety, tolerability and efficacy of combining IV pertuzumab with subcutaneous (SC) trastuzumab and a taxane, as 1st-line therapy in patients (pts) with HER2+ mBC. We present safety data with 19 months (mo) of median follow-up.
Methods: SAPPHIRE (NCT02019277) is a multicentre, open-label, phase IIIb study. Primary objective: safety and tolerability of IV pertuzumab + SC trastuzumab and investigator's choice of taxane. Pts ≥18 years with confirmed HER2+ mBC and ECOG PS 0-2 were included. The incidence and severity of adverse events (AEs), serious (S) AEs and AEs leading to premature discontinuation of study treatment were analyzed by taxane group.
Results: 50 pts enrolled in the study. Taxanes of choice: nab-paclitaxel (NP; n=36), docetaxel (D; n=13) and paclitaxel (P; n=1). As of March 4th 2016, 34 pts had withdrawn from study; median follow-up= 19mo (range: 6-27). 28(56%) pts received &gt;18 cycles of study medication. All patients experienced AEs with 326 AEs in the D group and 675 in the NP group; the majority being grade 1-2. The most common AEs were diarrhea, fatigue, peripheral neuropathy, alopecia, and rash. Grade 3+ AEs (n=77) were reported in 30 (60%) pts, 20 in the D group (8 pts; 62%) and 57 in the NP group (22 pts, 61%). The most common grade 3+ AEs in the D group were febrile neutropenia (4 pts, 31%) and neutropenia (3 pts; 23%); and in the NP group neutropenia (3 pts; 8%), anemia, diarrhea, cellulitis, peripheral neuropathy, LVEF decreased and pulmonary embolism each reported in 2(6%) pts . SAEs (n=44) were reported in 25(50%) pts, 11 (8 pts; 62%) in the D group and 33 (17 pts; 47%) in the NP group. The most common SAEs in the D group were febrile neutropenia (4 pts, 31%) and pyrexia (2 pts, 15%); and in the NP group: pyrexia (5 pts, 14%), cellulitis (2 pts, 6%) and pulmonary embolism (2 pts, 6%). AEs of suspected cardiac disorders (n=12) were reported in 7(14%) pts; atrial fibrillation, cardiomyopathy, myocardial ischemia, and dyspnea each reported in 1(2%) pt; and LVEF decreased, palpitation, hypertension each reported in 2(4%) pts. AEs leading to study drug discontinuation (n=6) were reported in 6(12%) pts [LVEF decreased (3), drug hypersensitivity, syncope and blister]. AEs leading to chemotherapy discontinuation (n=24) were reported in 10(20%) pts. 4(8%) pts died on study (disease progression).
Conclusion: No new safety signals have been reported in this study. Of further clinical interest is the finding that no cases of febrile neutropenia were reported in the NP taxane group compared to 4 in the D group. The safety profile remains consistent with the CLEOPATRA,1 PERUSE2 and HannaH3 studies, indicating the combination is safe and tolerable.
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2.Bachelot, et al. JCO 2014;32:5s(abstr#548)
3.Ismael, et al. Lancet Onc 2012;13:869.
Citation Format: Woodward N, De Boer RH, Redfern A, White M, Roberts W, Truman M, Beith J. Updated safety 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) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-31.