361PD - Interim Safety and Efficacy of Pertuzumab, Trastuzumab and Vinorelbine for First-Line (1L) Treatment of Patients (Pts) with Her2-Positive Locally Advanced or Metastatic Breast Cancer (Mbc)

Abstract

ABSTRACT Aim: 1L treatment of pts with HER2-positive MBC with vinorelbine (V) + trastuzumab (T) has similar efficacy to docetaxel (D) + T but with fewer adverse events (AEs) (the HERNATA study). Pertuzumab (P) + T + D significantly improves progression-free survival (PFS) and overall survival (OS) vs. T + D in 1L HER2-positive MBC (the CLEOPATRA study). VELVET is a Phase II study of P + T + V for 1L treatment of HER2-positive advanced breast cancer (BC), with Cohort 1 (C1) receiving P + T as separate infusions and Cohort 2 (C2) receiving P + T in a single saline infusion bag after the first cycle. Methods: Pts must have HER2-positive MBC or locally advanced BC and no prior non-hormonal anti-cancer therapy in the metastatic setting. The initial dose of P is 840 mg followed by 420 mg every 3 weeks (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 subsequent cycle Q3W. The primary endpoint is objective response rate based on best overall response. Secondary endpoints include PFS, OS and safety. Results: C1 and C2 are fully enrolled with 106 and 107 treated pts, respectively. At initial diagnosis, 32% (C1) and 25% (C2) of pts had MBC. In the neoadjuvant and adjuvant settings, 56% (C1) and 32% (C2) of pts had received chemotherapy, including a taxane (39% and 21%) or an anthracycline (39% and 26%); 41% and 18% had prior T exposure. At the data cut-off of 5 March 2014, the median number of cycles received in C1 was 15 for P + T and 9.5 for V, and in C2 was 10 for P + T and 9 for V. AEs were reported by 99% (C1) and 98% (C2) of pts. Grade ≥3 AEs were reported by 59% (C1) and 69% (C2) of pts. The grade ≥3 AEs in ≥5 pts in either cohort were neutropenia, leucopenia, diarrhoea, fatigue, febrile neutropenia, hypertension and asthenia. Serious AEs were reported by 29% (C1) and 33% (C2) of pts. Interim best overall response data from C1 will be presented. Conclusions: These interim safety data show that P + T + V has an acceptable AE profile with no unexpected safety signals. Administration of P + T sequentially, or in a single saline infusion bag, is feasible from a safety standpoint. Interim best overall response data from C1 will be presented. Disclosure: M. Andersson: has participated in an advisory board on behalf of Roche; T. Petit: has participated in an advisory board on behalf of Roche; U. Freudensprung: is an employee of Roche; S. Robb: is an employee of Roche; E. Restuccia: is an employee of and owns stocks in Roche. All other authors have declared no conflicts of interest.