TY - JOUR
T1 - Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration)
T2 - final results from a prospective, pooled analysis of six randomised, phase 3 trials
AU - André, Thierry
AU - Meyerhardt, Jeffrey
AU - Iveson, Timothy
AU - Sobrero, Alberto
AU - Yoshino, Takayuki
AU - Souglakos, Ioannis
AU - Grothey, Axel
AU - Niedzwiecki, Donna
AU - Saunders, Mark
AU - Labianca, Roberto
AU - Yamanaka, Takeharu
AU - Boukovinas, Ioannis
AU - Vernerey, Dewi
AU - Meyers, Jeffrey
AU - Harkin, Andrea
AU - Torri, Valter
AU - Oki, Eiji
AU - Georgoulias, Vassilis
AU - Taieb, Julien
AU - Shields, Anthony
AU - Shi, Qian
N1 - Funding Information:
TA reports personal fees from Amgen, Astra Zeneca, Bristol Myers Squibb (BMS), Chugai, Clovis Oncology, Gritstone Oncology, GlaxoSmithKline, Halliodx, Merck Sharp & Dohme (MSD), Tesaro, Pierre Fabre, Vantana, Servier, Sanofi, and Vantana, outside of the submitted work. IB reports personal fees from AstraZeneca, BMS, MSD, Novartis, Pfizer, Roche, Amgen, LEO Pharma, Pierre Fabre, and Boehringer Ingelheim; and personal fees from Sanofi, Servier, Lilly, and Regeneron, outside of the submitted work. AG reports grants, personal fees, and non-financial support from Bayer and Genentech; grants and personal fees from Array and Boston Biomedicals; and grants from OBI Pharmaceuticals and Merck, during the conduct of the study. TI reports honoraria from Eli Lilly, BMS, Bayer, Amgen, Roche, and Servier, during the conduct of the study. TYo reports grants from Novartis, MSK, Sumitomo Dainippon, Chugai Pharmaceutical, Sanofi, Daiichi Sankyo, Parexel, Ono Pharmaceutical, and GlaxoSmithKline, outside of the submitted work. EO reports personal fees from Yakult Honsha, Taiho Pharm, Bayer Yakuhin, Eli Lilly, Chugai Pharm, Ono Pharmaceutical, Takeda Pharm, and Merck, outside of the submitted work. TYa reports grants and personal fees from Chugai Pharmaceutical and Bayer; and grants from Takeda Pharmaceutical and Taiho Pharmaceutical, outside of the submitted work. JM reports personal fees from Taiho Pharmaceutical, Ignyta, and Cota Healthcare, outside of the submitted work. MS reports personal fees from Servier, Merck, and Amgen, outside of the submitted work. QS reports stocks from Merk, Johnson & Johnson, and Amgen; personal fees from Yiviva and Boehringer Ingelheim; and grants from Celgene and Genentech, outside of the submitted work. IS reports grants from Amgen and Roche; grants and personal fees from Merck South Africa and Sanofi; and personal fees from Servier, Ipsen, and MSD, outside of the submitted work. JT reports having a consulting or advisory role with and receiving honoraria from Amgen, Haliodx, MSD Oncology, AstraZeneca, Pierre Fabre, Roche, Sanofi, Lilly, Servier, and Merck; and has received travel and accommodation expenses from Genentech, Celgene, Pierre Fabre, Servier, and Merck. DV reports personal fees from GERCOR, Incyte, halioDx, and CellProthera, outside of the submitted work. All other authors declare no competing interests.
Funding Information:
The IDEA collaboration and the pooled analyses efforts were in part supported by a grant from the US National Cancer Institute (U10 CA180882). We dedicate this work to the memory of Daniel J Sargent.
PY - 2020/12
Y1 - 2020/12
N2 - Background: A prospective, pooled analysis of six randomised phase 3 trials was done to investigate disease-free survival regarding non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer; non-inferiority was not shown. Here, we report the final overall survival results. Methods: In this prospective, pooled analysis of six randomised phase 3 trials, we included patients with stage III colon cancer aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0–1 recruited between June 20, 2007, and Dec 31, 2015, across 12 countries in the CALGB/SWOG 80702, IDEA France, SCOT, ACHIEVE, TOSCA, and HORG trials, who started any treatment (modified intention-to-treat). Patients in all trials were randomly assigned to 3 months or 6 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) every 2 weeks or capecitabine and oxaliplatin (CAPOX) in different doses and methods every 3 weeks, at the treating physician's discretion. The primary endpoint was disease-free survival (time to relapse, secondary colorectal primary tumour, or death due to all causes), and overall survival (time to death due to all causes) was the prespecified secondary endpoint. The non-inferiority margin for overall survival was set as a hazard ratio (HR) of 1·11. Pre-planned subgroup analyses included regimen and risk group. Non-inferiority was declared if the one-sided false discovery rate adjusted (FDRadj) p value was less than 0·025. Findings: With median follow-up of 72·3 months (IQR 72·2–72·5), 2584 deaths among 12 835 patients were observed. 5064 (39·5%) patients received CAPOX and 7771 (60·5%) received FOLFOX. 5-year overall survival was 82·4% (95% CI 81·4–83·3) with 3 months of therapy and 82·8% (81·8–83·8) with 6 months of therapy (HR 1·02 [95% CI 0·95–1·11]; non-inferiority FDRadj p=0·058). For patients treated with CAPOX, 5-year overall survival was 82·1% (80·5–83·6) versus 81·2% (79·2–82·9; HR 0·96 [0·85–1·08]); non-inferiority FDRadj p=0·033), and for patients treated with FOLFOX 5-year overall survival was 82·6% (81·3–83·8) and 83·8% (82·6–85·0; HR 1·07 [0·97–1·18]; non-inferiority FDRadj p=0·34). Updated disease-free survival results confirmed previous findings (HR 1·08 [95% CI 1·02–1·15]; non-inferiority FDRadj p=0·25). Data on adverse events were not further recorded. Interpretation: Non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer was not confirmed in terms of overall survival, but the absolute 0·4% difference in 5-year overall survival should be placed in clinical context. Overall survival results support the use of 3 months of adjuvant CAPOX for most patients with stage III colon cancer. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies, and cost associated with a shorter treatment duration. Funding: US National Cancer Institute.
AB - Background: A prospective, pooled analysis of six randomised phase 3 trials was done to investigate disease-free survival regarding non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer; non-inferiority was not shown. Here, we report the final overall survival results. Methods: In this prospective, pooled analysis of six randomised phase 3 trials, we included patients with stage III colon cancer aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0–1 recruited between June 20, 2007, and Dec 31, 2015, across 12 countries in the CALGB/SWOG 80702, IDEA France, SCOT, ACHIEVE, TOSCA, and HORG trials, who started any treatment (modified intention-to-treat). Patients in all trials were randomly assigned to 3 months or 6 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) every 2 weeks or capecitabine and oxaliplatin (CAPOX) in different doses and methods every 3 weeks, at the treating physician's discretion. The primary endpoint was disease-free survival (time to relapse, secondary colorectal primary tumour, or death due to all causes), and overall survival (time to death due to all causes) was the prespecified secondary endpoint. The non-inferiority margin for overall survival was set as a hazard ratio (HR) of 1·11. Pre-planned subgroup analyses included regimen and risk group. Non-inferiority was declared if the one-sided false discovery rate adjusted (FDRadj) p value was less than 0·025. Findings: With median follow-up of 72·3 months (IQR 72·2–72·5), 2584 deaths among 12 835 patients were observed. 5064 (39·5%) patients received CAPOX and 7771 (60·5%) received FOLFOX. 5-year overall survival was 82·4% (95% CI 81·4–83·3) with 3 months of therapy and 82·8% (81·8–83·8) with 6 months of therapy (HR 1·02 [95% CI 0·95–1·11]; non-inferiority FDRadj p=0·058). For patients treated with CAPOX, 5-year overall survival was 82·1% (80·5–83·6) versus 81·2% (79·2–82·9; HR 0·96 [0·85–1·08]); non-inferiority FDRadj p=0·033), and for patients treated with FOLFOX 5-year overall survival was 82·6% (81·3–83·8) and 83·8% (82·6–85·0; HR 1·07 [0·97–1·18]; non-inferiority FDRadj p=0·34). Updated disease-free survival results confirmed previous findings (HR 1·08 [95% CI 1·02–1·15]; non-inferiority FDRadj p=0·25). Data on adverse events were not further recorded. Interpretation: Non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer was not confirmed in terms of overall survival, but the absolute 0·4% difference in 5-year overall survival should be placed in clinical context. Overall survival results support the use of 3 months of adjuvant CAPOX for most patients with stage III colon cancer. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies, and cost associated with a shorter treatment duration. Funding: US National Cancer Institute.
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U2 - 10.1016/S1470-2045(20)30527-1
DO - 10.1016/S1470-2045(20)30527-1
M3 - Article
C2 - 33271092
AN - SCOPUS:85096862943
VL - 21
SP - 1620
EP - 1629
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 12
ER -