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

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.