Oral vinorelbine in combination with trastuzumab as a first-line therapy of metastatic or locally advanced HER2-positive breast cancer.

Purpose: Vinorelbine-trastuzumab combination proved to be an effective first-line treatment for patients with locally advanced or metastatic breast cancer (MBC). Oral chemotherapy represents a step forward in MBC management. To improve patients' comfort using the oral form of vinorelbine, we conducted a multicenter phase II study to investigate the efficacy and safety of the oral vinorelbine-trastuzumab combination in women with MBC with human epidermal growth factor receptor 2 (HER2) overexpression.

Methods: Main eligibility criteria: HER2-positive disease, no adjuvant chemotherapy within the last 6 months and no prior chemotherapy for MBC. Patients were treated with oral vinorelbine 80 mg/m(2) D1, D8, D15 (following first 3 administrations at 60 mg/m(2) during the first cycle) for a total of 8 cycles (1 cycle = 3 weeks), in combination with trastuzumab 6 mg/kg on D1 (loading dose: 8 mg/kg) every 3 weeks or 4 mg/kg (loading dose: 6 mg/kg) weekly. Response was evaluated every 2 cycles using RECIST 1.0.

Primary Endpoint: objective response rate (ORR); secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results: In the full population (n = 26), median age was 50.7 years and median WHO PS 0. Median disease-free interval was 50.7 months [95 % CI (43.6-57.9)]. In the evaluable patients population, ORR was 56 % [95 % CI (34.9-75.6)], including 3 complete responses (12 %) and 11 partial (44 %); 8 (32 %) patients had stable disease resulting in a clinical benefit (or disease control) rate of 88 % [95 % CI (68.8-97.5)]. Median DOR was 7.1 months [95 % CI (3.9-10.2)], median PFS 6.7 months (95 % CI 3.5-10), and median OS 27.9 months (95 % CI 17.4-38.3). Treatment was generally well tolerated with main observed grade 3/4 hematological toxicities being neutropenia (46 %) and anemia (4 %). Grade 3-4 nausea-vomiting were observed in 11.5 % of patients.

Conclusions: Our results confirm the efficacy of oral vinorelbine-trastuzumab combination as a first-line treatment in HER2-positive locally advanced or MBC patients with an acceptable safety profile. Oral vinorelbine-trastuzumab optimizes the convenience of this chemotherapy regimen, especially for patients receiving trastuzumab every 3 weeks.