In an analysis of two trials (SCOT and IDEA-HORG) reported in the Journal of Clinical Oncology, Domingo et al identified the predictive value of Immunoscore for disease-free survival in patients with stage III colorectal cancer treated with adjuvant mFOLFOX6 (modified fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). Immunoscore predicts recurrence risk in early-stage colorectal cancer by quantifying CD3-positive and CD8-positive T-cell response in the core of the tumor and in the invasive margins.
Study Details
Among 3,061 patients with tumor samples, 2,643 had samples eligible for Immunoscore testing, including 1,792 who received CAPOX. Predefined cutoffs for Immunoscore, Immunoscore-Low and Immunoscore-High (combined Immunoscore-High and Immunoscore-Intermediate) were used for comparison of the two groups in analysis of disease-free survival.
Key Findings
Immunoscore was determined in 2,608 (99.5%) of patients with eligible samples, with 877 (33.7%) classified as Immunoscore-Low and 1,731 classified as Immunoscore-High. A total of 834 (32%) had received mFOLFOX6 and 1,774 (68%) had received CAPOX. Immunoscore-Low tumors were more commonly high-risk (T4 or N2; 52.9% vs 42.2% for Immunoscore-High, P < .001) and were more common in younger patients (P = .024).
For the Immunoscore-Low vs Immunoscore-High groups, 3-year disease free survival rates were 65.1% vs 79.4% in the mFOLFOX group, 69.8% vs 79.4% in the CAPOX group, and 68.6% vs 79.4% in the combined groups, respectively. In multivariate analysis, patients with Immunoscore-Low tumors had significantly shorter disease-free survival vs those with Immunoscore-High tumors (all P < .001) in the CAPOX group (HR = 1.52, 95% confidence interval [CI] = 1.28–1.82), mFOLFOX6 group (HR = 1.58, 95% CI = 1.22–2.04), and combined groups (HR = 1.55, 95% CI = 1.34–1.79), irrespective of sex, body mass index, clinical risk group, tumor location, treatment duration, or chemotherapy regimen.
In multivariate analysis of subgroups, Immunoscore was more strongly prognostic for disease-free survival in patients aged ≤ 65 years vs > 65 years in the CAPOX group, with hazard ratios of 1.92 (P < .001) vs 1.28 (P = .043; P for interaction = .026). Immunoscore was strongly prognostic among patients with DNA mismatch repair (MMR)-proficient status (HR = 1.68, P < .001) but not prognostic among those with MMR-deficient disease (HR = 0.67, P = .57; P for interaction = .03).
The addition of Immunoscore to a model containing all clinical variables significantly improved prediction of disease-free survival (P < .001) irrespective of MMR status.
The investigators concluded, “Immunoscore is prognostic in stage III colorectal cancer treated with FOLFOX or CAPOX, including within clinically relevant tumor subgroups. Possible variation in Immunoscore prognostic value by age and MMR status and prediction of benefit from extended adjuvant therapy merit validation.”
David N. Church, DPhil, of Oxford NIHR Comprehensive Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the UK Medical Research Council, Cancer Research UK, and others. For full disclosures of the study authors, visit ascopubs.org.
