Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes with 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin

Elisa Fontana*, Jeff Meyers, Alberto Sobrero, Timothy Iveson, Anthony F. Shields, Julien Taieb, Takayuki Yoshino, Ioannis Souglakos, Elizabeth C. Smyth, Florian Lordick, Markus Moehler, Anne Giraut, Andrea Harkin, Roberto Labianca, Jeffrey Meyerhardt, Thierry André, Ioannis Boukovinas, Sara Lonardi, Mark Saunders, Dewi VernereyEiji Oki, Vassilis Georgoulias, Irit Ben-Aharon, Qian Shi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)4009-4019
Number of pages11
JournalJournal of Clinical Oncology
Volume39
Issue number36
DOIs
StatePublished - 20 Dec 2021
Externally publishedYes

Funding

FundersFunder number
Agenzia Italiana del Farmaco
Gastrointestinal Track Cancer Group
Health Technology Assessment
Japanese Foundation for Multidisciplinary Treatment of Cancer
National Institute for Health Research, Efficacy and Mechanism Evaluation
National Cancer InstituteU10CA180882, CALGB/ SWOG 80702, UG1CA233163, U10CA180835, U10CA180888, U10CA180821
National Institute for Health and Care Research
Cancer Research UKEME 09/800/34, C1348/A15960
European Organisation for Research and Treatment of Cancer
Associazione Italiana per la Ricerca sul CancroIG21742-2018, FARM 5RWTWZ
Institut National du CancerPHRC2009
Agencia de Innovación y Desarrollo de Andalucía

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