title: Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial.
abstract: BACKGROUND
  The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned interim analysis of CLASSIC (median follow-up 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial.
  
  
  METHODS
  CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II-IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m(2) twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m(2) on day 1) for 6 months or observation alone. Randomisation was stratified by country and disease stage with a permuted block (size four) design. Neither patients nor investigators were masked to treatment assignment. The primary outcome was 3-year disease-free survival in the intention-to-treat population. This analysis presents the final preplanned assessment of outcomes after 5 years. The study is registered with ClinicalTrials.gov, NCT00411229.
  
  
  RESULTS
  We enrolled 1035 patients: 520 were randomly assigned to adjuvant capecitabine and oxaliplatin, and 515 to observation. Median follow-up for this analysis in the intention-to-treat population was 62·4 months (IQR 54-70). 139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio [HR] 0·58, 95% CI 0·47-0·72; p<0·0001). Estimated 5-year disease-free survival was 68% (95% CI 63-73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47-58) in the observation alone group. By the clinical cutoff date, 103 patients (20%) had died in the adjuvant capecitabine and oxaliplatin group versus 141 patients (27%) in the observation group (stratified HR 0·66, 95% CI 0·51-0·85; p=0·0015). Estimated 5-year overall survival was 78% (95% CI 74-82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64-73) in the observation group. Adverse event data were not collected after the primary analysis.
  
  
  CONCLUSIONS
  Adjuvant treatment with capecitabine plus oxaliplatin after D2 gastrectomy should be considered for patients with operable stage II or III gastric cancer.
  
  
  BACKGROUND
  F Hoffmann La-Roche and Sanofi.
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: sunghoonn@yuhs.ac.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.affiliation: Gastric Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.
authors.forename: Sook Ryun
authors.initials: SR
authors.lastname: Park
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Chonnam National University Hwasun Hospital, Jeonnam, South Korea.
authors.forename: Ik-Joo
authors.initials: IJ
authors.lastname: Chung
authors.affiliation: Department of Surgery, Yeungnam University College of Medicine, Daegu, South Korea.
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Hyung-Ho
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncology, Ajou University Hospital, Suwon, South Korea.
authors.forename: Jin-Hyuk
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, St Vincent's Hospital, Suwon, South Korea.
authors.forename: Hoon-Kyo
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Surgery, Kyungpook National University Medical Center, Daegu, South Korea.
authors.forename: Wansik
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Surgery, Korea Institute of Radiological and Medical Sciences, Korea Cancer Center, Seoul, South Korea.
authors.forename: Jong Inn
authors.initials: JI
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, Gachon University Gil Medical Center, Incheon, South Korea.
authors.forename: Dong Bok
authors.initials: DB
authors.lastname: Shin
authors.affiliation: Beijing Cancer Hospital, Beijing, China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University Taipei, Taoyuan, Taiwan.
authors.forename: Jen-Shi
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Clinical Research Division, Roche Korea, Seoul, South Korea.
authors.forename: Yunni
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Clinical Research Division, Roche Korea, Seoul, South Korea.
authors.forename: Stella
authors.initials: S
authors.lastname: Ha
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005500:Follow-Up Studies; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil