Multicenter phase II study of SOX plus trastuzumab for patients with HER2⁺ metastatic or recurrent gastric cancer: KSCC/HGCSG/CCOG/PerSeUS 1501B

Background: Trastuzumab (T-mab) combined with cisplatin and fluoropyrimidines is a standard first-line treatment for HER2⁺ advanced gastric cancer (AGC). We conducted the first phase II trial among four Japanese study groups to assess the efficacy and safety of T-mab + S-1 and oxaliplatin (T-SOX130) for HER2⁺ AGC or recurrent gastric cancer. Methods: Patients with IHC 3⁺ or IHC 2⁺/FISH⁺ tumors received 80 mg/m² (80–120 mg/day) oral S-1 on days 1–14, 130 mg/m² intravenous oxaliplatin on day 1, and intravenous T-mab (8 mg/kg loading dose, 6 mg/kg thereafter) on day 1 of a 21-day cycle. The primary endpoint was centrally assessed response rate (RR). Adverse events were based on the Common Terminology Criteria for Adverse Events (CTCAE) Ver.4.0. Results: We enrolled 42 patients from June 2015 to May 2016. Efficacy and safety analyses were conducted for 39 patients. The data cutoff was May 31, 2018. The confirmed RR was 82.1% (32/39; 90% CI 70.0–90.0); the disease control rate was 87.2% (34/39; 95% CI 73.3–94.4). Nine patients underwent curative surgery after T-SOX130. Median Time to treatment failure (TTF), Progression-free survival (PFS) and Overall survival (OS) was 5.7 (95% CI 4.6–7.0), 7.0 (95% CI 5.5–14.1), and 27.6 (95% CI 15.6–Not reached) months, respectively. Incidences of grade 3–4 adverse events > 10% were thrombocytopenia (17.9%), anorexia (17.9%), anemia (12.8%), neutropenia (10.3%), and hyponatremia (10.3%). Conclusions: T-SOX130 showed promising response and survival with a favorable safety profile and should be considered for patients with HER2⁺ AGC.