We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Association of Age With Treatment-Related Adverse Events and Survival in Patients With Metastatic Colorectal Cancer.
- Authors
Meng, Lingbin; Thapa, Ram; Delgado, Maria G.; Gomez, Maria F.; Ji, Rui; Knepper, Todd C.; Hubbard, Joleen M.; Wang, Xuefeng; Permuth, Jennifer B.; Kim, Richard D.; Laber, Damian A.; Xie, Hao
- Abstract
Key Points: Question: Is there any difference in treatment-related adverse events and outcomes between patients with early-onset (age <50 years) and older patients with metastatic colorectal cancer (mCRC)? Findings: In this cohort study of 1223 patients with mCRC from 3 clinical trials, early-onset mCRC had significantly worse survival and displayed unique patterns of treatment-related adverse events. Analysis in a separate Moffitt Cancer Center cohort of 736 patients noted worse overall survival in early-onset mCRC and showed distinct genomic profiles in this population, which may partially explain the disparity. Meaning: These findings might have utility for an individualized approach to chemotherapy, counseling, and management of treatment-related adverse events in patients with early-onset mCRC. Importance: While the incidence of early-onset metastatic colorectal cancer (mCRC) has been increasing, studies on the age-related disparity in this group of patients are limited. Objective: To evaluate the association of age with treatment-related adverse events and survival in patients with mCRC and explore the potential underlying factors. Design, Setting, and Participants: This cohort study included 1959 individuals. Individual data on 1223 patients with mCRC who received first-line fluorouracil and oxaliplatin therapy in 3 clinical trials, and clinical and genomic data of 736 patients with mCRC from Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort. All statistical analyses were conducted from October 1, 2021, through November 12, 2022. Exposures: Metastatic colorectal cancer. Main Outcomes and Measures: Survival outcomes and treatment-related adverse events were compared among patients in 3 age groups: younger than 50 (early onset), 50 to 65, and older than 65 years. Results: In the total population of 1959 individuals, 1145 (58.4%) were men. Among 1223 patients from previous clinical trials, 179 (14.6%) in the younger than 50 years group, 582 (47.6%) in the 50 to 65 years group, and 462 (37.8%) in the older than 65 years group had similar baseline characteristics except for sex and race. The younger than 50 years group had significantly shorter progression-free survival (PFS) (hazard ratio [HR], 1.46; 95% CI, 1.22-1.76; P <.001) and overall survival (OS) (HR, 1.48; 95% CI, 1.19-1.84; P <.001) compared with the 50 to 65 years group after adjustment for sex, race, and performance status. Significantly shorter OS in the younger than 50 years group was confirmed in the Moffitt cohort. The younger than 50 years group had a significantly higher incidence of nausea and vomiting (69.3% vs 57.6% [50-65 years] vs 60.4% [>65 years]; P =.02), severe abdominal pain (8.4% vs 3.4% vs 3.5%; P =.02), severe anemia (6.1% vs 1.0% vs 1.5%; P <.001), and severe rash (2.8% vs 1.2% vs 0.4% P =.047). The younger than 50 years group also had earlier onset of nausea and vomiting (1.0 vs 2.1 vs 2.6 weeks; P =.01), mucositis (3.6 vs 5.1 vs 5.7 weeks; P =.05), and neutropenia (8.0 vs 9.4 vs 8.4 weeks; P =.04), and shorter duration of mucositis (0.6 vs 0.9 vs 1.0 weeks; P =.006). In the younger than 50 years group, severe abdominal pain and severe liver toxic effects were associated with shorter survival. The Moffitt genomic data showed that the younger than 50 years group had a higher prevalence of CTNNB1 mutation (6.6% vs 3.1% vs 2.3%; P =.047), ERBB2 amplification (5.1% vs 0.6% vs 2.3%; P =.005), and CREBBP mutation (3.1% vs 0.9% vs 0.5%; P =.05), but lower prevalence of BRAF mutation (7.7% vs 8.5% vs 16.7%; P =.002). Conclusions and Relevance: In this cohort study of 1959 patients, those with early-onset mCRC showed worse survival outcomes and unique adverse event patterns, which could be partially attributed to distinct genomic profiles. These findings may inform individualized management approaches in patients with early-onset mCRC. This cohort study compares survival outcomes and adverse event patterns among patients with early-onset metastatic colorectal cancer with those of older patients.
- Subjects
THERAPEUTIC use of antineoplastic agents; RESEARCH; SPECIALTY hospitals; CONFIDENCE intervals; NAUSEA; MUCOSITIS; GENETIC mutation; AGE distribution; LOG-rank test; METASTASIS; ANTINEOPLASTIC agents; EXANTHEMA; FISHER exact test; COLORECTAL cancer; FLUOROURACIL; TREATMENT effectiveness; RISK assessment; CANCER patients; CANCER treatment; COMPARATIVE studies; VOMITING; HEPATOTOXICOLOGY; DESCRIPTIVE statistics; ANEMIA; CHI-squared test; KAPLAN-Meier estimator; RESEARCH funding; OXALIPLATIN; DRUG side effects; STATISTICAL correlation; PROGRESSION-free survival; ABDOMINAL pain; DATA analysis software; LONGITUDINAL method; OVERALL survival
- Publication
JAMA Network Open, 2023, Vol 6, Issue 6, pe2320035
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2023.20035