Abstract P2-16-10: Safety of pertuzumab plus trastuzumab plus vinorelbine for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer
Authors: Perez EA , López-Vega JM , Del Mastro L , Petit T , Zamagni C , Freudensprung U , Bastière-Truchot L , Walker R , Andersson M 
Published: August 2014

Abstract
Background: HER2 overexpression or amplification, occuring in ∼15-20% of breast cancers (BC), is associated with a poor prognosis. Trastuzumab (T) and pertuzumab (P) are humanized monoclonal antibodies that bind to different HER2 epitopes, inhibiting HER2 signaling. It was previously shown that first-line (1L) treatment of patients (pts) with HER2-positive metastatic breast cancer (MBC) with vinorelbine (V)+T had similar efficacy to docetaxel+T, but with fewer adverse events (AEs) (HERNATA). In a recent study, P+T+docetaxel significantly improved progression-free survival (PFS) and overall survival (OS) compared with T+docetaxel in pts with HER2-positive 1L MBC (CLEOPATRA). The objective of the VELVET study is to investigate the efficacy and safety of P+T+V for 1L treatment of HER2-positive MBC.
Methods: This is a multicenter, open-label, single-arm, two-cohort, Phase II study. The recruitment target is 105 pts per cohort. Pts in Cohort 1 receive P+T+V as separate infusions. Pts in Cohort 2 receive P+T from a single infusion bag followed by V. The initial dose of P is 840 mg, followed by 420 mg q3w; the initial dose of T is 8 mg/kg, followed by 6 mg/kg q3w; V is administered at 25 mg/m2 in Cycle 1, followed by 30-35 mg/m2, on Days 1 and 8 of each cycle, q3w. Pts must have HER2-positive MBC or locally advanced BC (LABC) and a baseline left ventricular ejection fraction (LVEF) of ≥55%. Previous treatment with systemic nonhormonal anticancer therapy in the metastatic setting is not allowed. The primary endpoint is independently assessed overall response rate. Secondary endpoints include PFS, OS, and safety.
Results: Interim safety data are presented for Cohort 1; 106 pts were enrolled. Median age at screening was 56 years. Median interval between initial BC diagnosis and enrollment was 2.6 years. 33% of pts had Stage IV BC at initial BC diagnosis. At diagnosis of advanced disease, 13% and 87% of pts had LABC and MBC, respectively. 54% of pts had previously received chemotherapy, including taxane (38%) and anthracycline (36%). 41% had prior T exposure. A median of 6 cycles of P, T, and V was received at the time of this analysis. An AE overview is shown in the table.
Pts, n(%)N = 106Any AE102(96)Grade 338(36)Grade 417(16)Grade 52(2)aAny serious AE25(24)Most frequent (≥4 pts) grade ≥3 AEs Neutropeniab21(20)Febrile neutropenia6(6)Leukopenia5(5)Asthenia4(4)Constipation4(4)Diarrhea4(4)a Myocardial infarction and septic shock; b Covers ‘neutropenia’ and ‘neutrophil count decreased’
Grade ≥3 neutropenia/febrile neutropenia was experienced by 8% of pts in Cycle 1 and by 14% of pts in Cycle 2; this proportion decreased during subsequent cycles. There was no overall decrease in mean LVEF from baseline.
Conclusions: The combination of P+T+V was well tolerated; no new safety signals were observed. The incidences of grade ≥3 neutropenia, febrile neutropenia, and leukopenia were lower than those previously observed in pts with HER2-positive MBC treated with 1L P+T+docetaxel in CLEOPATRA or those treated with T+V in HERNATA; however, it should be noted that the treatment period in these two studies was longer. Efficacy data for Cohorts 1 and 2 will be reported at the end of the study.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-10.