Comparing five-weekly S-1 plus cisplatin with tri-weekly capecitabine plus cisplatin in patients with HER2-negative recurrent gastric cancer after S-1 adjuvant therapy or chemotherapy naïve advanced gastric cancer: A pooled analysis of HERBIS-2 (OGSG 1103) and HERBIS-4A (OGSG 1105) trials.

Abstract

379 Background: HERBIS-2 trial was a phase II trial where S-1 plus cisplatin (SP) and capecitabine plus cisplatin (XP) were compared in recurrent HER2 negative gastric cancer (GC) patients with recurrence free interval (RFI) by S-1containing adjuvant of ≥ 6 months. We performed pooled analyses of HERBIS-2 and HERBIS-4A trial where SP and XP were compared in chemotherapy-naive HER2 negative gastric cancer (GC) patients as these trials being identical. Methods: Both HERBIS-2 and 4A trials, patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2twice daily for 14 days plus cisplatin 80 mg/m2on day 1, every 3 weeks). Results: In HERBIS-2 which was s closed early due to poor accrual, SP ( N= 10) tended to confer a better overall survival (OS) compared with XP ( N= 9)[18.7 (95%CI, 2.8 – NR) months vs.13.4 (95% CI, 5.2 – 31.3) months; hazard ratio (HR), 0.443 (95% CI, 0.156 – 1.258); P= .117]. In pooled analyses with HERBIS-2 and 4A, SP ( N= 50) vs. XP ( N = 51) showed longer progression free survival (6.4 vs.5.1 months; HR, 0.666; P= .62), OS (14.8 vs. 10.6 months; HR, 0.695; P= .099), time to treatment failure (4.6 vs. 3.6 months; HR, 0.668; P= .045), and higher disease control rate (86.4% vs. 68.1%, P= .149). Subgroup analysis revealed that OS benefit in SP arm compared to XP arm was significantly larger if the patient having PS of 0 [HR, 0.554 (95% CI, 0.309 to 0.959; interaction P= .035], or the tumor arising from upper area of stomach [HR, 0.266 (95% CI, 0.070 to 0.731); interaction P= .013] or harboring differentiated type cancer [HR, 0.433 (95% CI, 0.228 to 0.822); interaction P= .011], respectively. Conclusions: Our data suggest the use of SP in the 1stline setting in HER2 negative advanced or recurrent GC with RFI by S-1 adjuvant of ≥ 6 months. Pooled analyses further suggest SP as the standard 1st line chemotherapy for HER2 negative AGC irrespective of S-1 adjuvant in Japan. Clinical trial information: UMIN000006755/UMIN000006105.