Phase II Prospective Study of Trastuzumab in Combination with S-1 and Oxaliplatin (SOX100) Therapy for HER2-Positive Advanced Gastric Cancer.

ABSTRACT

PURPOSE: The standard first-line treatment for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer (AGC) is trastuzumab in combination with cisplatin and fluoropyrimidines. We evaluated the efficacy and safety of S-1 and oxaliplatin (100 mg/m2) (SOX100) combined with trastuzumab, a monoclonal antibody against HER2 for HER2-positive AGC. METHODS: In this single-arm, multicenter phase II study, patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, oxaliplatin (100 mg/m2) intravenously on day 1, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. RESULTS: A total of 25 patients from six centers were enrolled from December 2015 to March 2020. In the 25 patients evaluable for analysis, the 1-year survival rate was 70.8% [90% confidence interval (CI) = 55.5-86.1%], whereas the median OS, PFS, and ORR were 17.8 (95% CI 10.5-22.9) months, 7.6 (95% CI 5.0-10.9) months, and 75.0% (95% CI 53.3-90.2), respectively. Major grade 3/4 adverse events included anorexia (20%), anemia (16%), peripheral sensory neuropathy (16%), and diarrhea (15%). CONCLUSION: SOX100 combined with trastuzumab was effective with a favorable safety profile in patients with HER2-positive AGC.