Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin
Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin
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 = .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 = .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.
4009-4019
Fontana, Elisa
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Meyers, Jeff
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Sobrero, Alberto
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Iveson, Timothy
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Shields, Anthony F
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Taieb, Julien
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Yoshino, Takayuki
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Souglakos, Ioannis
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Smyth, Elizabeth C
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Lordick, Florian
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Moehler, Markus
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Giraut, Anne
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Harkin, Andrea
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Labianca, Roberto
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Meyerhardt, Jeffrey
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André, Thierry
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Boukovinas, Ioannis
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Lonardi, Sara
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Saunders, Mark
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Vernerey, Dewi
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Oki, Eiji
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Georgoulias, Vassilis
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Ben-Aharon, Irit
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Shi, Qian
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20 December 2021
Fontana, Elisa
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Meyers, Jeff
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Sobrero, Alberto
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Iveson, Timothy
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Shields, Anthony F
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Taieb, Julien
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Yoshino, Takayuki
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Souglakos, Ioannis
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Smyth, Elizabeth C
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Lordick, Florian
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Moehler, Markus
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Giraut, Anne
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Harkin, Andrea
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Labianca, Roberto
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Meyerhardt, Jeffrey
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André, Thierry
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Boukovinas, Ioannis
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Lonardi, Sara
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Saunders, Mark
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Vernerey, Dewi
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Oki, Eiji
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Georgoulias, Vassilis
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Ben-Aharon, Irit
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Shi, Qian
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Fontana, Elisa, Meyers, Jeff, Sobrero, Alberto, Iveson, Timothy, Shields, Anthony F, Taieb, Julien, Yoshino, Takayuki, Souglakos, Ioannis, Smyth, Elizabeth C, Lordick, Florian, Moehler, Markus, Giraut, Anne, Harkin, Andrea, Labianca, Roberto, Meyerhardt, Jeffrey, André, Thierry, Boukovinas, Ioannis, Lonardi, Sara, Saunders, Mark, Vernerey, Dewi, Oki, Eiji, Georgoulias, Vassilis, Ben-Aharon, Irit and Shi, Qian
(2021)
Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 39 (36), .
(doi:10.1200/JCO.21.02008).
Abstract
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 = .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 = .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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Accepted/In Press date: 14 October 2021
e-pub ahead of print date: 9 November 2021
Published date: 20 December 2021
Additional 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.
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Local EPrints ID: 454857
URI: http://eprints.soton.ac.uk/id/eprint/454857
ISSN: 1527-7755
PURE UUID: 9857c5e6-676d-4fd7-8303-41118bb471a5
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Date deposited: 28 Feb 2022 17:31
Last modified: 17 Mar 2024 02:45
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Contributors
Author:
Elisa Fontana
Author:
Jeff Meyers
Author:
Alberto Sobrero
Author:
Anthony F Shields
Author:
Julien Taieb
Author:
Takayuki Yoshino
Author:
Ioannis Souglakos
Author:
Elizabeth C Smyth
Author:
Florian Lordick
Author:
Markus Moehler
Author:
Anne Giraut
Author:
Andrea Harkin
Author:
Roberto Labianca
Author:
Jeffrey Meyerhardt
Author:
Thierry André
Author:
Ioannis Boukovinas
Author:
Sara Lonardi
Author:
Mark Saunders
Author:
Dewi Vernerey
Author:
Eiji Oki
Author:
Vassilis Georgoulias
Author:
Irit Ben-Aharon
Author:
Qian Shi
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