The incidence of metastatic colorectal cancer (mCRC) among adults younger than 50 years has been increasing, and although younger patients are treated with aggressive regimens similarly to older patients, outcomes data, including incidence of toxic effects, across age groups are limited, wrote Lingbin Meng, MD, of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., and colleagues, in their paper on the new research.
“Studies on the age-related disparity ... provided mixed findings,” said corresponding author Hao Xie, MD, of the Mayo Clinic in Rochester, Minn., in an interview.
According to the paper, published in JAMA Network Open, the researchers sought to evaluate the association between age and mCRC treatment-related adverse events and survival.
The study population included 1,223 mCRC patients who underwent first-line treatment with fluorouracil and oxaliplatin therapy in three clinical trials. An additional 736 patients with mCRC from the Moffitt Cancer Center were used to assess genomic alterations and serve as an external validation cohort.
Methods and results
Patients were divided into three age groups: younger than 50 years, 50-65 years, and 65 years and older. Early onset was defined as younger than 50 years. Approximately 58% of the study population was male.
The primary outcomes were treatment-related adverse events and survival rates. Overall survival (OS) and progression-free survival (PFS) were was significantly shorter in the early-onset group, compared with the 50-65 years group (hazard ratios, 1.48 and 1.46, respectively, P < .001 for both) in a multivariate analysis. The shorter OS in the early-onset group was confirmed in the validation cohort.
The early-onset patients had significantly higher incidence of nausea and vomiting, severe abdominal pain, severe anemia, and severe rash, compared with patients in both the 50- to 65-year-old group and the older than 65 years group. In addition, abdominal pain and severe liver toxicity effects were associated with shorter survival in the early-onset patients.
Genomic data from the Moffitt cohort showed a higher prevalence of CTNNB1 mutation among patients younger than 50 years, compared with the 50- to 65-year-old group and the older than 65 years group (6.6%, 3.1%, and 2.3%, respectively; P = .047), as well as ERBB2 amplification (5.1%, 0.6%, and 2.3%, respectively; P = .005), and CREBBP mutation (3.1%, 0.9%, and 0.5%; P = .05), although the prevalence of BRAF mutation was significantly lower in the younger patients, compared with patients in the older groups (7.7%, 8.5%, and 16.7%, respectively; P = .002).
These data suggest that distinct genomic profiles may play a role in the worse outcomes for patients with early-onset mCRC, the researchers said.
The findings were limited by several factors, including the timing of the trials prior to the use of biologics as standard first-line therapy, the researchers noted. Other limitations include a lack of data on treatment adherence and intensity and the location and number of metastases, and potential limited generalizability to other populations given that the majority of the participants were white, they said.
