First-line treatment of HER2-positive metastatic breast cancer (HER2+MBC) with trastuzumab, doectaxel and vinorelbine: results of a Minnie Pearl Cancer Research Network trial

BACKGROUND: Vinorelbine and docetaxel plus trastuzumab show synergy in the preclinical setting. A randomized clinical trial has shown that addition of trastuzumab to docetaxel improves all clinical outcomes without adding to the toxicity profile of docetaxel alone. A number of phase II trials of trastuzumab plus vinorelbine have demonstrated good efficacy and minimal toxicity with this combination. Combining more than two agents has the potential to further enhance efficacy. We investigated the feasibility and safety of the triple combination of trastuzumab, docetaxel and vinorelbine as first-line therapy of HER2+ MBC. METHODS: Patients with previously untreated, measurable, HER2+ MBC (IHC 3+ [HercepTest®] and/or FISH+) were eligible. Eligibility criteria also included an ECOG score of 0-2 and normal baseline LVEF. Patients received vinorelbine (25mg/m²) and docetaxel (30mg/m²) on days 1 and 8, q3w. Trastuzumab was given weekly (4mg/kg loading dose followed by 2 mg/kg/wk). RESULTS: 40 patients have been enrolled. Median age is 58 years (range 41-79). 29 patients had IHC 3+ disease, 12 patients FISH+ disease. 13 patients had received prior therapy, including 9 treated with taxanes. The majority of patients had >2 organ sites of metastasis; the most common site was the lungs. 34 patients are evaluable for response. The response rate is 70% with 13 (38%) partial responses and 11 (32%) complete responses. Median progression-free survival is 17.1 months. A median of 6 cycles (range 2-16) of treatment were administered, with 225 cycles evaluable for toxicity. Neutropenia was the most commonly reported grade 3/4 toxicity (24%); 19% patients experienced febrile neutropenia. Other grade 3/4 toxicities included fatigue (11%), hyperglycaemia (11%), and myalgias (5%). There were 3 deaths due to intercurrent illnesses (myocardial infarction, renal failure, and pneumonia). CONCLUSION: First-line therapy with the combination of trastuzumab, vinorelbine and docetaxel in patients with HER2+ MBC is effective with manageable toxicity. Recruitment continues and updated results will be presented.