TY - JOUR
T1 - Early-Onset Colorectal Adenocarcinoma in the IDEA Database
T2 - Treatment Adherence, Toxicities, and Outcomes with 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin
AU - Fontana, Elisa
AU - Meyers, Jeff
AU - Sobrero, Alberto
AU - Iveson, Timothy
AU - Shields, Anthony F.
AU - Taieb, Julien
AU - Yoshino, Takayuki
AU - Souglakos, Ioannis
AU - Smyth, Elizabeth C.
AU - Lordick, Florian
AU - Moehler, Markus
AU - Giraut, Anne
AU - Harkin, Andrea
AU - Labianca, Roberto
AU - Meyerhardt, Jeffrey
AU - André, Thierry
AU - Boukovinas, Ioannis
AU - Lonardi, Sara
AU - Saunders, Mark
AU - Vernerey, Dewi
AU - Oki, Eiji
AU - Georgoulias, Vassilis
AU - Ben-Aharon, Irit
AU - Shi, Qian
N1 - Funding Information:
Supported by European Organisation for Research and Treatment of Cancer EORTC-GITCG-RP 2009 Prof Irit Ben-Aharon; Japanese Foundation for Multidisciplinary Treatment of Cancer and Yakult Konsha Co Ltd ACHIEVE clinical Trial; National Cancer Institute NCI, CALGB/ SWOG 80702 clinical trial, U10CA180821, U10CA180835, UG1CA233163, U10CA180882, and U10CA180888; HORG Foundation HORG clinical trial; Institut National du Cancer and Programme Hospitalier de Recherche Clinique en Cancérologie, IDEA clinical trial, PHRC2009; Agenzia Italiana del Farmaco and AIRC TOSCA, clinical trial, FARM 5RWTWZ and AIRC IG21742-2018; National Institute for Health Research, Efficacy and Mechanism Evaluation, the National Institute for Health Research, Health Technology Assessment, and Cancer Research United Kingdom SCOT clinical trial, EME 09/800/34 and C1348/A15960. This work is dedicated to the memory of Daniel J. Sargent. Dan was one of the world’s foremost experts in biostatistics and oncology who brought together disparate investigators and established data sharing across academia and industry internationally. His groundbreaking initiatives of integrating large collections of databases enabled research to answer questions otherwise beyond statistical possibility, to design important new clinical studies, to make regulatory observations, and to set new standards. He pushed these innovations farther to prospectively plan internationally combined analyses that answered questions previously believed to be impossible. The world of oncology statistics and analysis will not be the same without him, but his legacy continues. The authors acknowledge all the authors who contributed to the clinical trials included in the IDEA academic collaboration and the Gastrointestinal Track Cancer Group at the European Organisation for Research and Treatment of Cancer (EORTC) for funding.
Funding Information:
Supported by European Organisation for Research and Treatment of Cancer EORTC-GITCG-RP 2009 Prof Irit Ben-Aharon; Japanese Foundation for Multidisciplinary Treatment of Cancer and Yakult Konsha Co Ltd ACHIEVE clinical Trial; National Cancer Institute NCI, CALGB/ SWOG 80702 clinical trial, U10CA180821, U10CA180835,
Funding Information:
This work is dedicated to the memory of Daniel J. Sargent. Dan was one of the world’s foremost experts in biostatistics and oncology who brought together disparate investigators and established data sharing across academia and industry internationally. His groundbreaking initiatives of integrating large collections of databases enabled research to answer questions otherwise beyond statistical possibility, to design important new clinical studies, to make regulatory observations, and to set new standards. He pushed these innovations farther to prospectively plan internationally combined analyses that answered questions previously believed to be impossible. The world of oncology statistics and analysis will not be the same without him, but his legacy continues. The authors acknowledge all the authors who contributed to the clinical trials included in the IDEA academic collaboration and the Gastrointestinal Track Cancer Group at the European Organisation for Research and Treatment of Cancer (EORTC) for funding.
Publisher Copyright:
© 2022 American Society of Clinical Oncology. All rights reserved
PY - 2021/12/20
Y1 - 2021/12/20
N2 - PURPOSE Early-onset (EO) colorectal cancer (CRC, age, 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age $ 50 years). MATERIALS AND METHODS Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non–cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P, .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P 5 .97), higher N2 disease rate (24% v 22%, P, .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P, .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value, .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value, .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value 5 .85). CONCLUSION Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.
AB - PURPOSE Early-onset (EO) colorectal cancer (CRC, age, 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age $ 50 years). MATERIALS AND METHODS Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non–cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P, .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P 5 .97), higher N2 disease rate (24% v 22%, P, .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P, .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value, .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value, .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value 5 .85). CONCLUSION Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.
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U2 - 10.1200/JCO.21.02008
DO - 10.1200/JCO.21.02008
M3 - Article
C2 - 34752136
AN - SCOPUS:85122772900
SN - 0732-183X
VL - 39
SP - 4009
EP - 4019
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 36
ER -