Vinflunine in combination with trastuzumab for treatment of HER2-positive metastatic breast cancer

Abstract

1058 Background: Vinflunine (VFL) is a microtubule inhibitor of the vinca alkaloid class with high activity in several tumour types especially in second line treatment of metastatic breast cancer (MBC). Over-expression of HER2 is observed in 20–25% of all breast cancers and is associated with a poor prognosis. The development of the anti-HER2 therapy with trastuzumab (T) allowed significant prolonging of the survival in HER2 positive MBC. The combination of these two compounds which are separately active in MBC warranted a combination study. Methods: This phase I was designed to determine the recommended dose (RD) of VFL in combination with T for treatment of first or second line MBC patients (pts), to assess its safety profile, and to determine its antitumour activity. Results: Thirty pts, median age 55 [33–74] years, WHO performance status 0/1: 18/12 pts , respectively were given VFL 280 mg/m2 (10 pts) or 320 mg/m2 (20 pts) day 1 every 3 weeks (w) in combination with T (loading dose 4 mg/kg and subsequently 2 mg/kg/w). Six pts were chemonaive and 5 pts received this combination in second line. At the first VFL dose (280 mg/m2), 0/6 pts experienced dose-limiting toxicity. The RD was established at 320 mg/m2 in the following 6 pts. All 30 pts are evaluable for safety. Haematological toxicities were: anaemia grade (G) 3: 0 and 1 pt; neutropenia G 3/4: 5/17 pts, febrile neutropenia 0/2 pts with VFL 280 and 320 mg/m2, respectively. G 3 non-haematological adverse events were only reported in the 20 pts receiving VFL 320 mg/m2: fatigue and myalgia: 5 pts; constipation: 4 pts; abdominal pain, neutropenic infection: 2 pts. ileus, hyponatremia, arthralgia: 1 pt. No significant cardiac events were observed. The response rates, 62.5% [95% confidence interval: 24.5–91.5] and 73.7% [95% confidence interval: 48.8–90.9] in pts receiving VFL at 280 mg/m2 and 320 mg/m2 respectively, were established by an external radiologist using RECIST in the first 27 evaluable patients. Conclusions: Vinflunine/trastuzumab combination is feasible with encouraging response rates and manageable toxicity in MBC pts. A phase III study comparing VFL + T versus paclitaxel + T has been initiated. No significant financial relationships to disclose.