Sung Hoon Noh1, Sook Ryun Park2, Han-Kwang Yang3, Hyun Cheol Chung4, Ik-Joo Chung5, Sang-Woon Kim6, Hyung-Ho Kim7, Jin-Hyuk Choi8, Hoon-Kyo Kim9, Wansik Yu10, Jong Inn Lee11, Dong Bok Shin12, Jiafu Ji13, Jen-Shi Chen14, Yunni Lim15, Stella Ha15, Yung-Jue Bang16. 1. Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: sunghoonn@yuhs.ac. 2. Gastric Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, South Korea. 3. Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea. 4. Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. 5. Department of Internal Medicine, Chonnam National University Hwasun Hospital, Jeonnam, South Korea. 6. Department of Surgery, Yeungnam University College of Medicine, Daegu, South Korea. 7. Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea. 8. Department of Hematology-Oncology, Ajou University Hospital, Suwon, South Korea. 9. Department of Internal Medicine, St Vincent's Hospital, Suwon, South Korea. 10. Department of Surgery, Kyungpook National University Medical Center, Daegu, South Korea. 11. Department of Surgery, Korea Institute of Radiological and Medical Sciences, Korea Cancer Center, Seoul, South Korea. 12. Department of Hematology-Oncology, Gachon University Gil Medical Center, Incheon, South Korea. 13. Beijing Cancer Hospital, Beijing, China. 14. Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University Taipei, Taoyuan, Taiwan. 15. Clinical Research Division, Roche Korea, Seoul, South Korea. 16. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
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 oxaliplatingroup 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.
RCT Entities:
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.
Authors: Don S Dizon; Lada Krilov; Ezra Cohen; Tara Gangadhar; Patricia A Ganz; Thomas A Hensing; Stephen Hunger; Smitha S Krishnamurthi; Andrew B Lassman; Merry Jennifer Markham; Erica Mayer; Michael Neuss; Sumanta Kumar Pal; Lisa C Richardson; Richard Schilsky; Gary K Schwartz; David R Spriggs; Miguel Angel Villalona-Calero; Gina Villani; Gregory Masters Journal: J Clin Oncol Date: 2016-02-04 Impact factor: 44.544
Authors: Florian Bösch; Rumyana Todorova; Helena Link; C Benedikt Westphalen; Stefan Boeck; Volker Heinemann; Jens Werner; Thomas Kirchner; Martin K Angele; Jens Neumann Journal: J Cancer Res Clin Oncol Date: 2019-09-20 Impact factor: 4.553