In a pooled analysis reported in the Journal of Clinical Oncology, Cohen et al found that the addition of oxaliplatin to fluoropyrimidine was associated with improved overall and disease-free survival in patients with stage III colon cancer with microsatellite instability (MSI). They also found the combination improved overall survival in patients with MSI vs microsatellite-stable (MSS) disease among those with N1—but not N2—disease.

Study Details

The study included individual patient data on 5,457 patients with available MSI and MSS status from 12 randomized trials in the ACCENT (Adjuvant Colon Cancer End Points) database, including 609 (11.2%) with MSI and 4,848 (88.8%) with MSS. Analyses were adjusted for demographic and clinicopathologic factors. A total of 4,250 patients received oxaliplatin and fluoropyrimidine, including 461 MSI patients and 3,789 MSS patients.

Key Findings

In pooled analysis of two trials directly assessing fluoropyrimidine with vs without oxaliplatin, the addition of oxaliplatin in MSI patients (n = 185) was associated with significantly improved overall survival (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.2–0.93) and disease-free survival (adjusted HR = 0.47, 95% CI = 0.27–0.82). Among 1,440 MSS patients, the adjusted hazard ratios were 0.89 (95% CI = 0.74–1.06) and 0.82 (95% CI = 0.70–0.97), respectively.

Pooled analysis among the 4,250 patients receiving the combination showed that MSI vs MSS status was associated with improved overall survival among 2,645 patients with N1 disease (adjusted HR = 0.66, 95% CI = 0.46–0.95) but not among 1,605 patients with N2 disease (adjusted HR = 1.13, 95% CI = 0.86–1.48). Similar outcomes were found for disease-free survival.  

Among the 461 MSI patients receiving the combination, significant independent prognostic factors for overall survival were N stage (N2 vs N1; HR = 3.10, 95% CI = 2.13–4.50), T stage (T4 vs T1–3; HR = 2.39, 95% CI = 1.56–3.66), and sex (male vs female; HR = 1.71, 95% CI = 1.14–2.58). Similar findings were made for disease-free survival.

The investigators concluded, “Adding oxaliplatin to fluoropyrimidine improves overall survival and disease-free survival in patients with MSI stage III colon cancer. Compared with MSS, MSI patients experienced better outcomes in the N1 group but similar survival in the N2 group.”

Romain Cohen, MD, PhD, of Sorbonne Université, Department of Medical Oncology, Saint-Antoine Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Cancer Institute, ARCAD foundation, Nuovo-Soldati Foundation, ARC Foundation for Cancer Research, and Servier Institute. For full disclosures of the study authors, visit ascopubs.org.