Does oxaliplatin benefit come with an age limit in patients with stage II or III colorectal cancer (CRC)?
New data from a population-based cohort show that adding oxaliplatin chemotherapy to fluoropyrimidine in the adjuvant setting significantly improved survival in patients with stage III CRC up to age 70 but not those older than age 70. The analysis also revealed that the drug did not improve survival in those with stage II disease, regardless of patients' age.
"The findings suggest that oxaliplatin may benefit patients aged 70 years or younger with stage III colorectal cancer, while its use in patients aged older than 70 years and those with stage II disease warrants reconsideration," according to the study authors, led by Jun Woo Bong, MD, PhD, of Korea University Guro Hospital in Seoul, Republic of Korea.
Oxaliplatin-based chemotherapy is standard for patients with stage II to III CRC following surgery, but its benefit in older patients remains unclear, with studies yielding conflicting results. A large retrospective study, for instance, found overall survival improved with oxaliplatin-based adjuvant therapy in patients older than age 70 with stage III disease, while an analysis of three studies did not find a survival benefit associated with oxaliplatin in older patients.
The latest analysis, published online in JAMA Network Open, aimed to clarify how, or whether, age should factor into treatment decisions.
Bong and colleagues conducted a population-based retrospective cohort study using data from the Korea Health Insurance Review and Assessment Service's National Quality Assessment program. The researchers included 8561 patients who underwent curative resection for stage II and stage III CRC and received adjuvant chemotherapy between January 2014 and December 2016. The patients were followed until April 2024 or death.
The research team primarily looked at overall survival, assessing age thresholds from 60 to 80 years to identify an age cutoff for a survival benefit. The team also evaluated discontinuation rates.
For the 2913 patients with stage II disease, the researchers did not identify an age threshold where oxaliplatin was associated with improved overall survival. Across all age thresholds, oxaliplatin was not linked to better survival outcomes among patients with stage II disease (adjusted hazard ratios [AHRs] ranged from 0.71 to 1.09).
In contrast, oxaliplatin was associated with significantly improved overall survival among patients with stage III disease aged 70 years or younger (AHR, 0.59), with a significantly higher 5-year overall survival rate in the oxaliplatin group (84.8% vs 78.1% in the fluoropyrimidine only group). After age 70, oxaliplatin was not associated with improved overall survival (AHR, 0.85; 95% CI, 0.67-1.07; P = .18), with similar 5-year overall survival rates in both groups (71% vs 68%).
In patients with stage III disease, discontinuation rates continuously increased from ages 60 to 80 and was significantly higher among patients older than 70 years -- 37.4% vs 23.9% among younger patients (adjusted odds ratio, 1.55; P < .001). Discontinuation was also associated with worse overall survival (AHR, 1.54).
The discontinuation data suggest that "older patients may experience greater difficulty tolerating oxaliplatin-based regimens" potentially affecting treatment efficacy, Alfonso De Stefano, MD, PhD, of Istituto Nazionale Tumori at Fondazione G. Pascale in Naples, Italy, and colleagues wrote in an accompanying editorial.
And the findings overall indicate "clinicians may need to be more cautious when recommending oxaliplatin for patients older than 70 years or those with stage II disease," according to De Stefano and colleagues wrote.
Even with the age-focused findings, the researchers noted that age should not be the only consideration when weighing the risks and benefits of oxaliplatin in this population.
"Studies have suggested that biological age, which includes factors such as frailty and organ function, may be more relevant than chronological age in predicting chemotherapy outcomes," Bong and colleagues wrote.
De Stefano and colleagues agreed, noting that clinicians should consider factors beyond age, such as comorbidities, cognitive function, social and economic conditions, and mobility.
"We need to be cautious that we don't interpret the results as an age threshold," said Nadine Jackson , MD, MPH, of Harvard Medical School and Dana-Farber Cancer Institute, Boston.
Jackson, who was not involved in the research, recommended against changes to practice guidelines or clinical decision-making based on age before prospective data becomes available.
"As clinicians, we all need to recognize that older adults are the patients who are most likely to be seen and diagnosed with cancer, and there can be complicated care outcomes as a result," said Jackson. "This isn't some other doctor's problem -- this is where oncology is. We need to support geriatric skills for both practicing oncologists and trainees so we can listen to our patients and determine what to prioritize for their care."
This study was supported and funded by a Korean University Guro Hospital grant, as well as grants from the Institute of Information & Communications Technology Planning & Evaluation, Korean Ministry of Science, Korea Health Industry Development Institute, and Korean Ministry of Health & Welfare. Bong and colleagues reported no disclosures, and De Stefano and colleagues reported nonfinancial support, personal fees, and grants outside of the commentary. Jackson reported no relevant disclosures.