A comprehensive population-based study from Korea has revealed that oxaliplatin-based adjuvant chemotherapy provides survival benefits only in select colorectal cancer patients, specifically those with stage III disease aged 70 years or younger. The research, published in JAMA Network Open, challenges current treatment approaches for older patients and those with stage II disease.
Age-Specific Survival Benefits in Stage III Disease
The study analyzed 8,561 patients with stage II to III colorectal cancer who underwent curative surgery and received adjuvant chemotherapy between January 2014 and December 2016. Among patients with stage III disease aged 70 years or younger, oxaliplatin was associated with significantly improved survival, with an adjusted hazard ratio (AHR) of 0.59 (95% CI, 0.46-0.77; P < .001).
The survival advantage translated to meaningful clinical outcomes, with 5-year overall survival rates of 84.8% in the oxaliplatin group versus 78.1% in the non-oxaliplatin group (P = .003). After propensity score matching, the benefit remained consistent, with 5-year survival rates of 85.0% versus 78.9% (P = .01).
Limited Benefit in Older Patients
In stark contrast, patients older than 70 years with stage III disease showed no survival benefit from oxaliplatin therapy. The AHR for this population was 0.85 (95% CI, 0.67-1.07; P = .18), with 5-year survival rates of 68.3% versus 70.6% (P = .36) for oxaliplatin versus non-oxaliplatin groups, respectively.
"This study found no association of oxaliplatin use with improved survival in patients older than 70 years," the researchers noted. "This highlights the importance of refining age thresholds and incorporating geriatric assessments into treatment planning to identify patients who are likely to benefit from aggressive regimens."
Treatment Tolerability Concerns
The study revealed significant tolerability issues in older patients. Among those older than 70 years with stage III disease, the chemotherapy discontinuation rate was 37.4% compared to 23.9% in patients 70 years or younger (P < .001). Within the older population, discontinuation rates were higher in the oxaliplatin group (39.9%) versus the non-oxaliplatin group (33.4%, P = .008).
Oxaliplatin use in older patients was associated with a higher risk of chemotherapy discontinuation, with an adjusted odds ratio of 1.55 (95% CI, 1.19-2.03; P = .001).
No Benefit in Stage II Disease
The research found no survival benefit from oxaliplatin in patients with stage II colorectal cancer at any age threshold. Adjusted hazard ratios ranged from 0.71 (95% CI, 0.34-1.50) to 1.09 (95% CI, 0.73-1.64) across different age groups, with none reaching statistical significance.
"In patients with stage II disease, the lack of association between oxaliplatin and improved survival highlights the need for refined risk stratification to guide adjuvant therapy decisions," the researchers emphasized.
Study Population and Methodology
The study utilized data from the Korea Health Insurance Review and Assessment Service, examining outcomes in 5,648 patients with stage III disease and 2,913 patients with stage II disease. The mean age was 63.2 years, with 59.4% being male. Researchers compared outcomes between oxaliplatin-based regimens (including CAPOX, FOLFOX, and modified FOLFOX) and fluoropyrimidine alone treatments.
To determine optimal age cutoffs, the researchers assessed age thresholds from 60 to 80 years, ultimately identifying 70 years as the most clinically relevant boundary for treatment decisions.
Clinical Implications
The findings suggest that current treatment guidelines may need revision to better account for age-specific benefits and risks. The study indicates that 8.9% of patients 70 years and younger received non-oxaliplatin treatment compared with 38.6% of patients older than 70 years, suggesting some clinical awareness of age-related considerations.
"Future research should continue to explore innovative approaches to optimize the treatment of older patients with colorectal cancer to ensure a balance between efficacy and safety," the researchers concluded, acknowledging study limitations including potential selection bias and lack of molecular data or adverse event reporting.
