Trastuzumab with cisplatin and fluoropyrimidines(FUs) improved the overall survival of patients with human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer (AGC). S-1 plus oxaliplatin (SOX) is a one of the standard regimen for HER2-negative AGC especially in Japan. However, to date, few studies have evaluated the efficacy and safety of trastuzumab combined with SOX in patients with HER2-positive AGC.
This is the multi-central, phase II study that is conducted in 10 Japanese institutions. Patients with HER2-positive AGC received S-1 (80mg/m2) twice a day orally on days 1–14, oxaliplatin (130mg/m2) intravenously on day 1, and trastuzumab (course 1, 8mg /kg; course 2-, 6mg/kg) intravenously on day 1 of a 21-day cycle. The primary end point was confirmed response rate (cRR); secondary end points included overall survival (OS), progression-free survival(PFS), and adverse events.The sample size was determined to be 75cases based on a hypothesis of threshold RR of 50% and an expected RR of 65%, 90% power, with an alpha value of 0.1 (one-sided) using the binomial test.
From June 2015 to January 2018, a total of 78 patients were screened, of whom 75 were enrolled and eligible. The median age was 64 years. ECOG PS(0/1);57/18, unresectable/recurrence; 66/9, Gastric/EGJ; 64/11, pathology(tub1/tub2/por/sig); 13/33/24/5, metastatic sites(LNs/liver/peritoneum/lung/bone/others); 40/35/20/9/3/8. The proportion of IHC 3+ was 73.3%. In the full analysis set of 75 patients as of March 2018, cRR was 65.2% (95% confidence interval (CI).52.4–76.5); n = 66: excluding unconfirmed 9 cases; and the disease control rate was 89.4% (95% CI.79.4-95.6). Median OS, PFS, were estimated as 20.6 (95% CI.14.8–30.6) and 9.4(95% CI.7.4-14.7) months, respectively. Major grade 3 or 4 adverse events included sensory neuropathy (14.7%), neutropenia (9.3%), diarrhea (6.7%), and anemia (6.7%). There were no treatment-related deaths.
Trastuzumab in combination with SOX showed promising activity with well-tolerated toxicities in patients with HER2-positive AGC as well as other platinum and FUs. Final analysis based on confirmed response will be reported at the conference.
Clinical trial identification
Legal entity responsible for the study
Japanese Foundation for Multidisciplinary Treatment of Cancer.
A. Takashima: Grants: Gilead Sciences, Takeda Pharmaceutical Company; Personal fees: Takeda Pharmaceutical Company, Taiho Pharmaceutical Co., Ltd, Merck, Chugai Pharmaceutical Company P, Sanofi K.K., outside the submitted work. S. Kadowaki: Grants: Boehringer Ingelheim, Taiho Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Eli Lilly Japan. T. Nishina: Grants, Honoraria: Taiho Pharmaceutical, Chugai Pharmaceutical. T.E. Nakajima: Personal financial interests: Eli Lilly, Sanofi, Chugai, Sawai, Bayer, Bristol, Taiho, Merck, Ono, Takeda, Mochida, MSD; Institutional financial interests: Ono, Taiho, A2 Health Care, JCRO, Daiichi-Sankyo, Mediscience Planning. D. Takahari: Honoraria: Taiho Pharmaceutical, Eli Lilly Japan, Chugai Pharmaceutical, Yakult Honsha. All other authors have declared no conflicts of interest.