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. FINDINGS: 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.

INTERPRETATION: Adjuvant treatment with capecitabine plus oxaliplatin after D2

gastrectomy should be considered for patients with operable stage II or III

gastric cancer. FUNDING: F Hoffmann La-Roche and Sanofi.