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 Anticancer Agents
Gastric Cancer
Biological Therapy
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.