Efficacy and Tolerability of First-Line Cetuximab Plus Leucovorin, Fluorouracil, and Oxaliplatin (FOLFOX-4) Versus FOLFOX-4 in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The Open-Label, Randomized, Phase III TAILOR Trial

Abstract

Purpose: Cetuximab in combination with chemotherapy is a standard-of-care first-line treatment regimen for patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC); however, the efficacy of cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX) has never before been proven in a controlled and randomized phase III trial. To our knowledge, the TAILOR trial ( ClinicalTrials.gov identifier: NCT01228734) is the first randomized, multicenter, phase III study of the addition of cetuximab to first-line FOLFOX prospectively choosing a RAS wt population and thus providing confirmative data for the efficacy and safety of cetuximab plus FOLFOX versus FOLFOX alone.

Patients and methods: TAILOR is an open-label, randomized (1:1), multicenter, phase III trial in patients from China comparing FOLFOX-4 with or without cetuximab in RAS wt (KRAS/NRAS, exons 2 to 4) mCRC. The primary end point of TAILOR was progression-free survival time; secondary end points included overall survival time, overall response rate, and safety and tolerability.

Results: In the modified intent-to-treat population of 393 patients with RAS wt mCRC, adding cetuximab to FOLFOX-4 significantly improved the primary end point of progression-free survival time compared with FOLFOX-4 alone (hazard ratio, 0.69; 95% CI, 0.54 to 0.89; P = .004; median, 9.2 v 7.4 months, respectively), as well as the secondary end points of overall survival time (current assessment after 300 events: hazard ratio, 0.76; 95% CI, 0.61 to 0.96; P = .02; median, 20.7 v 17.8 months, respectively) and overall response rate (odds ratio, 2.41; 95% CI, 1.61 to 3.61; P < .001; 61.1% v 39.5%, respectively). Treatment was well tolerated, and there were no new or unexpected safety findings.

Conclusion: The TAILOR study met all of its objectives and relevant clinical end points, confirming cetuximab in combination with FOLFOX as an effective standard-of-care first-line treatment regimen for patients with RAS wt mCRC.

Figures

Fig 1.

TAILOR study patient disposition. (*) One patient randomly assigned to the leucovorin, fluorouracil, and oxaliplatin (FOLFOX-4) arm received cetuximab plus FOLFOX-4; this patient was included in the FOLFOX-4 arm of the mITT population considered for efficacy analysis but the cetuximab plus FOLFOX-4 arm of the modified safety population considered for safety analysis. ITT, intent to treat; mITT, modified intent to treat; wt, wild type.

Fig 2.

(A) Primary end point of progression-free survival (PFS) time by independent review committee in the RAS wild-type modified intent-to-treat population. (B) Secondary end point of overall survival (OS) time in the RAS wild-type modified intent-to-treat population. FOLFOX-4, leucovorin, fluorouracil, and oxaliplatin; HR, hazard ratio.

Fig 3.

Forest plot of demographic- and biomarker-defined subgroup analyses involving the primary end point of progression-free survival time by independent review committee in the RAS wild-type modified intent-to-treat population. BSA, body surface area; EGFR, epidermal growth factor receptor; FOLFOX-4, leucovorin, fluorouracil, and oxaliplatin; HR, hazard ratio; LDH, lactate dehydrogenase; M-184/3Nos, adenocarcinoma, not otherwise specified; ULN, upper limit of normal.