Phase II Study of S-1 in Combination with Trastuzumab for HER2-positive Metastatic Breast Cancer

Aim: We undertook a prospective phase II study to evaluate the efficacy of S-1 plus trastuzumab combination regimen for human epidermal-growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: HER2-positive MBC patients received oral administration of S-1 (80 mg/m 2 /day, days 1 to 28, every 6 weeks) and intravenous weekly trastuzumab (2 mg/kg), according to the results of a prior Phase I trial of our group. Results: A total of 28 patients were enrolled and received a median of 3.5 (range 1-10) cycles of treatment. Overall response rate and clinical benefit rate were 53.6% and 75.0%, respectively. Progression-free survival was 30 weeks. With regard to grade 3 and 4 adverse effects, leucopenia, neutropenia, increase in serum alanine aminotransferase, and diarrhea were observed. Conclusion: Combination of S- 1 and trastuzumab was tolerable and had excellent efficacy with good response and disease control in this trial. Trastuzumab, a humanized monoclonal antibody against the extracellular domain of human epidermal growth factor receptor type-2, has shown high clinical efficacy in combination with cytotoxic agents for HER2-overexpressing breast cancer. After this agent was approved, prognosis of the patients with HER2- positive advanced or metastatic disease has become superior to that of estrogen receptor-negative disease (1). According to the Japanese Breast Cancer Society guidelines (2) and National Comprehensive Cancer network guidelines (3) chemotherapy is recommended for advanced or metastatic breast cancer that is refractory to hormonal therapy. The first and second choices of cytotoxic agents are either anthracyclines or taxanes. The options for the third-line or later treatment comprised of capecitabine, S-1, vinorelbine, irinotecan, gemcitabine, and eribulin. For HER2-positive