First-Line EGFR Inhibitor Plus FOLFOX4 in RAS Wild-Type Metastatic Colorectal Cancer
In the Chinese phase III TAILOR trial reported in the Journal of Clinical Oncology, Qin et al found that adding the EGFR inhibitor cetuximab to FOLFOX4 (fluorouracil, leucovorin, oxaliplatin) improved progression-free survival in patients with RAS wild-type metastatic colorectal cancer.
Study Details
In the open-label multicenter trial, initiated in 2010, 393 patients with RAS wild-type metastatic colorectal cancer (modified intent-to-treat population; 504 patients with wild-type KRAS disease were enrolled) were randomized to receive cetuximab plus FOLFOX4 (n = 193) or FOLFOX4 alone (n = 200).
The primary endpoint was progression-free survival in the modified intent-to-treat population on independent review committee assessment.
Efficacy Outcomes
Median follow-up was 44.4 months in the cetuximab group and 48.7 months in the FOLFOX4 alone group. Median progression-free survival was 9.2 months in the cetuximab group vs 7.4 months in the FOLFOX4 alone group (hazard ratio [HR] = 0.69, P = .004). On investigator assessment, median progression-free survival was 9.2 vs 7.4 months (HR = 0.65, P < .001). Median overall survival (assessed after 300 events) was 20.7 months vs 17.8 months (HR = 0.76, P = .02). Overall response rates were 61.1% vs 39.5% (odds ratio = 2.41, P < .001).
Adverse Events
The most common grade ≥ 3 adverse events in both the cetuximab and control groups were neutropenia (61.9% vs 43.2%) and leukopenia (26.8% vs 21.1%). Grade ≥ 3 febrile neutropenia occurred in 1% of both groups. Grade ≥ 3 skin reactions occurred in 25.8% vs 0% of patients. Serious adverse events occurred in 19.1% vs 13.1% of patients. Adverse events led to discontinuation of cetuximab in 16.0% of patients and to discontinuation of FOLFOX4 in 39.2% vs 27.1%. Adverse events led to death in eight patients in the cetuximab group and five patients in the control group.
The investigators concluded, “The TAILOR study met all of its objectives and relevant clinical endpoints, confirming cetuximab in combination with FOLFOX as an effective standard-of-care first-line treatment regimen for patients with RAS [wild-type] metastatic colorectal cancer.”
The study was supported by Merck KGaA.
Jin Li, MD, of the Shanghai East Hospital of Tongji University, is the corresponding author of the Journal of Clinical Oncology article.
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