Oxaliplatin Elicits Improved Survival in Select Patients with Stage III CRC

After propensity score matching, the association of oxaliplatin with OS in the fully adjusted model of patients 70 years and younger was significant, but in those older than 70 years, oxaliplatin was not associated with improved survival.

The addition of oxaliplatin to fluoropyrimidine-based adjuvant chemotherapy in select older patients with stage III colorectal cancer (CRC) exhibited improved survival outcomes vs chemotherapy alone, according to findings from a population-based retrospective cohort study published in JAMA Open Network.¹

Specifically, patients 70 years and younger with stage III disease saw an adjusted HR (AHR) for oxaliplatin use with overall survival (OS) of 0.79 (95% CI, 0.63-0.99; P = .04). By contrast, patients 70 years and older and those with stage II disease ages 60 to 80 years old (AHR, range, 0.71 [95% CI, 0.34-1.50] to 1.09 [95% CI, 0.73-1.64]) were not associated with improved survival vs without oxaliplatin.

Furthermore, in a fully age-adjusted model of patients 70 years or younger with stage II disease, the AHR for the association of oxaliplatin use with OS was 0.59 (95% CI, 0.46-0.77; P < .001). For patients older than 70 years, oxaliplatin was not associated with improved OS in any model (AHR, 0.85; 95% CI, 0.67-1.07; P = .18). Additionally, after propensity score matching (PSM), the association of oxaliplatin with OS in the fully adjusted model of patients 70 years and younger was 0.60 (95% CI, 0.41-0.89; P = .01). Further, in those older than 70 years, oxaliplatin was not associated with improved survival in any model.

In the stage III disease, 70 years and younger group before PSM, the 5-year OS in the oxaliplatin and non-oxaliplatin arms was 84.8% vs 78.1% (P = .003). Furthermore, after PSM in the respective treatment populations, the 5-year OS was 85.0% vs 78.9% (P = .01). Additionally, for the older than 70 group, the respective 5-year rates were 68.3% vs 70.6% (P = .36) before PSM and 68.0% vs 71.0% (P = .29) after PSM.

“In this cohort study, oxaliplatin was associated with improved OS among patients with stage III colorectal cancer aged 70 years or younger but not among patients older than 70 years or patients with stage II disease,” Jun Woo Bong, MD, PhD, of the Department of Surgery, Korea University Guro Hospital in Seoul, Republic of Korea, wrote in the publication with study coinvestigators. “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. 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.”

Using data from the Korea Health Insurance Review and Assessment Service National Quality Assessment (HIRA-NQA) program, the population-based, retrospective cohort study included patients who underwent curative radical resection for stage II or III CRC and received adjuvant chemotherapy between January 2014 and December 2016. In total, 2913 patients with stage II disease and 5648 patients with stage III disease were included.

The study specifically examined outcomes associated with adjuvant non-oxaliplatin regimens, comprised of fluorouracil plus leucovorin (folinic acid) or capecitabine, vs adjuvant oxaliplatin regimens, which included capecitabine plus oxaliplatin (CAPOX), fluorouracil/leucovorin plus oxaliplatin (FOLFOX), and modified FOLFOX.

Across the combined analysis cohort, the mean age was 63.2 years (SD, 11.2), 59.4% were male, and greater proportions of female patients, those who were obese, those who used oxaliplatin-based regimens, and patients who discontinued chemotherapy were higher in the stage II disease group. Oral capecitabine use was more frequent in the stage III disease vs stage II disease groups (23.6% vs 21.6%; P = .04). Furthermore, 8.9% of those 70 years and younger received non-oxaliplatin treatment compared with 38.6% of patients older than 70 years.

The rate of chemotherapy discontinuation among patients older than 70 years with stage III disease was 37.4% vs 23.9% among patients 70 years or younger (P < .001). Furthermore, the rate of chemotherapy discontinuation among patients older than 70 years was 39.9% in the oxaliplatin group vs 33.4% in the non-oxaliplatin group, achieving statistical significance (P = .008). A nonsignificant difference with observed in the 70 and younger group, at 24.2% vs 20.7%, respectively (P = .17).

Reference

Bong JW, Lee H, Jeong S, Kang S. Older age threshold for oxaliplatin benefit in stage II to III colorectal cancer. JAMA Open Netw. 2025;8(8):e2525660. doi:10.1001/jamanetworkopen.2025.25660