668PD - Non inferiority analysis of multicenter phase III comparing cisplatin/S-1 (CS) with cisplatin/5-FU (CF) as first-line therapy in patients with advan...

Date 01 October 2012
Event ESMO Congress 2012
Session Gastrointestinal tumors, non-colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Gastric Cancer
Presenter Jaffer Ajani
Authors J.A. Ajani1, W. Rodriguez Pantigoso2, G. Bodoky3, V. Moiseyenko4, M. Lichinitser5, V.A. Gorbunova5, I. Vynnychenko6, I. Láng7, S. Falcon1
  • 1Gastrointestinal Medical Oncology, MD Anderson, Cancer center, 77030 - Houston/US
  • 2Oncologia Y Radioterapia, Instituto de Oncologia Y RadioterapiaClinica Rica, Clinica Vesa, PE-27 - Lima/PE
  • 3Department Of Oncology, St.László Hospital, Budapest/HU
  • 4N.N.Petrov Research Inst. of Oncology, RU-197758 - St. Petersburg/RU
  • 5Department Of Chemotherapy, N. N. Blokhin Russian Cancer Research Center, RU-115478 - Moscow/RU
  • 6Medical Oncology, Sumy Regional Oncology Centre, Sumy/UA
  • 7Dept. Med. Oncology And Clin. Pharmacology B, St.László Hospital, Budapest/HU




S-1, a new generation of oral fluoropyrimidine, is active against Advanced Gastric Cancer (AGC). The primary analysis of FLAGS (JCO 2010; vol.28 p 1547-53) did not show any differences in overall survival (OS) between CS and CF. S-1 has been registered in Europe, with supportive analyses including non-inferiority (NI) analysis.


1,053 (1,029 treated; CS = 521/CF = 508) patients (non Asian 88 + %) with untreated, advanced gastric (83.1 %) / gastroesophageal (16.5%) adenocarcinoma were randomized to either S-1 (25 mg/m2 bid, d 1-21)/cisplatin (75 mg/m2 d 1) q 28 d or 5-FU (1,000 mg/m2/d1-5 infusion)/cisplatin (100 mg/m2 d 1) q 28 d. OS analyses for non-inferiority, by pre-specified stratifications, were performed.


OS for NI from CS (8.6 months) compared to CF (7.9 months) had a HR = 0.92 (two-sided 95% CI, 0.80-1.05). HR = 1.05 being lower than HR = 1.10 non inferiority margin, derived from a literature meta-analysis, CS remains statistically significantly non-inferior (p = 0.0068) to CF. The 74% preserved control effect by CS is well above the suggested 50% by Rothmann et al. (Statist-Med2003; 22:239-264), based on which the 1.10 non-inferiority margin was derived. Moreover, statistically significant safety advantages for the CS arm were observed for the rates of G3/4 neutropenia (18.6%, CS; 40.0%, CF), G3/4 febrile neutropenia (1.7%, CS; 6.9%, CF), G3/4 stomatitis (1.3%, CS; 13.6%, CF), renal adverse events (all grades: 18.8%, CS; 33.5%, CF), and severe hypokalemia (3.6%, CS; 10.8%, CF). On the other safety items, no significant differences were noted between CS and CF, especially regarding Head and Foot Syndrome which was anecdotal and limited to grade 1/2. Treatment-related deaths were significantly reduced with CS compared to CF (respectively 2.5% and 4.9%).


CS is non-inferior to CF while providing safety advantages for the patients and is a treatment alternative in advanced gastric carcinoma.


All authors have declared no conflicts of interest.