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.

• Authors: Shukui Qin, Jin Li, Liwei Wang, Jianming Xu, Ying Cheng, Yuxian Bai, Wei Li, Nong Xu, Li-Zhu Lin, Qiong Wu, Yunfeng Li, Jianwei Yang, Hongming Pan, Xuenong Ouyang, Wensheng Qiu, Kaichun Wu, Jianping Xiong, Guanghai Dai, Houjie Liang, Chunhong Hu, Jun Zhang, Min Tao, Qiang Yao, Junyuan Wang, Jiongjie Chen, S Peter Eggleton, Tianshu Liu
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 36 Issue 30 Pg. 3031-3039 (10 20 2018) ISSN: 1527-7755 [Electronic] United States
• PMID: 30199311 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Organoplatinum Compounds
• Cetuximab
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cetuximab (administration & dosage, adverse effects)
• China
• Colorectal Neoplasms (drug therapy, mortality)
• Female
• Fluorouracil (therapeutic use)
• Humans
• Leucovorin (therapeutic use)
• Male
• Middle Aged
• Organoplatinum Compounds (therapeutic use)
• Progression-Free Survival
• Young Adult