Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC)

5-year follow-up of an open-label, randomised phase 3 trial

CLASSIC trial investigators

Research output: Contribution to journalArticle

286 Citations (Scopus)

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/m2 twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m2 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.

Original languageEnglish
Pages (from-to)1389-1396
Number of pages8
JournalThe Lancet Oncology
Volume15
Issue number12
DOIs
Publication statusPublished - 2014 Jan 1

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oxaliplatin
Gastrectomy
Stomach Neoplasms
Observation
Disease-Free Survival
Capecitabine
Republic of Korea

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

@article{c800e0e6ce4d44abb459121b64df83b0,
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/m2 twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m2 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.",
author = "{CLASSIC trial investigators} and Noh, {Sung Hoon} and Park, {Sook Ryun} and Yang, {Han Kwang} and Hyuncheol Chung and Chung, {Ik Joo} and Kim, {Sang Woon} and Kim, {Hyung Ho} and Choi, {Jin Hyuk} and Kim, {Hoon Kyo} and Wansik Yu and Lee, {Jong Inn} and Shin, {Dong Bok} and Jiafu Ji and Chen, {Jen Shi} and Yunni Lim and Stella Ha and Bang, {Yung Jue}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/S1470-2045(14)70473-5",
language = "English",
volume = "15",
pages = "1389--1396",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "12",

}

Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC) : 5-year follow-up of an open-label, randomised phase 3 trial. / CLASSIC trial investigators.

In: The Lancet Oncology, Vol. 15, No. 12, 01.01.2014, p. 1389-1396.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC)

T2 - 5-year follow-up of an open-label, randomised phase 3 trial

AU - CLASSIC trial investigators

AU - Noh, Sung Hoon

AU - Park, Sook Ryun

AU - Yang, Han Kwang

AU - Chung, Hyuncheol

AU - Chung, Ik Joo

AU - Kim, Sang Woon

AU - Kim, Hyung Ho

AU - Choi, Jin Hyuk

AU - Kim, Hoon Kyo

AU - Yu, Wansik

AU - Lee, Jong Inn

AU - Shin, Dong Bok

AU - Ji, Jiafu

AU - Chen, Jen Shi

AU - Lim, Yunni

AU - Ha, Stella

AU - Bang, Yung Jue

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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/m2 twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m2 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.

AB - 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/m2 twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m2 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.

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U2 - 10.1016/S1470-2045(14)70473-5

DO - 10.1016/S1470-2045(14)70473-5

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SP - 1389

EP - 1396

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

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