Updated analysis of a phase II study of SOX plus trastuzumab for the patients with HER2 positive advanced or recurrent gastric cancer: KSCC/HGCSG/CCOG/PerSeUS1501B

Abstract

Background: Trastuzumab (T-mab) combined with cisplatin and fluoropyrimidines is the standard first line treatment for the patients with HER2-positive advanced gastric cancer (AGC). We conducted first phase II trial to assess the efficacy and safety of Tmab combined with S-1 and oxaliplatin (HER-SOX130) for HER2-positive AGC or recurrent gastric cancer. Method(s): Patients with IHC 3+ or IHC 2+/FISH positive received 80 mg/m2 (80- 120 mg/body) S-1 per day orally on days 1-14, 130 mg/m2 oxaliplatin intravenously on day 1, and T-mab (8-mg/kg loading dose and 6 mg/kg thereafter) intravenously on day 1 of a 21-day cycle until one of the criteria for withdrawal of the study treatment occurred. The primary end-point was the response rate (RR). The secondary endpoints were adverse events, progression-free survival (PFS), overall survival (OS), timeto- treatment failure (TTF), duration of treatment, time to failure of strategy (TFS) and dose intensity. Adverse events were recorded based on the CTCAE Ver.4.0. Result(s): 42 patients were enrolled from June 2015 to May 2016. Efficacy and safety analyses were conducted in the full analysis set of 39 patients. The data cut off specific to the survival status was February 19, 2018. The proportion of patients with IHC 3+ was 87%. The incidence of grade 3 or 4 adverse events (>10%) were platelet count decreased (17.9%), anorexia (17.9%), neutrophil count decreased (12.8%), anemia (10.3%), and hyponatremia (10.3%). The confirmed RR assessed by the independent review committee was 82.1%(32/39) (95%C.I.: 67.3-91.0), and the disease control rate was 87.2%(34/39) (95%C.I.: 73.3-94.4). 9 cases underwent curative surgery after HERSOX130. Median PFS, TTF and OS was 7.0 (95%C.I.: 5.5-14.1), 5.7 (95%C.I.: 4.6-7.0) and 27.7 (95%C.I.: 15.6-) months, respectively. Conclusion(s): HER-SOX130 demonstrates promising response and survival with avourable safety profile. HER-SOX130 should be considered for the patients with HER2-positive AGC.