A phase I/II study of cetuximab in combination with 5-fluorouracil (5-FU)/folinic acid (FA) plus weekly oxaliplatin (L-OHP) (FUFOX) in the first-line treatment of patients with metastatic colorectal cancer (mCRC) expressing epidermal growth factor receptor (EGFR). Preliminary results

Abstract

3644 Background: Cetuximab (Erbitux) is an EGFR-targeting IgG1 monoclonal antibody that showed in combination with 5-FU/FA/L-OHP (FOLFOX4) one of the highest response rates ever reported in 1st-line treatment of mCRC. Methods: This phase I/II trial of standard dose cetuximab in combination with L-OHP and infusional 5-FU/FA in a weekly schedule (AIO FUFOX protocol) was conducted in order to investigate the recommended dose and the efficacy of this combination at the respective dose level. In the phase I part cetuximab and L-OHP/FA were given at their fixed doses while two dose levels of 5-FU were investigated (cetuximab 400 mg/m2 i.v. in week 1 followed by 250 mg/m2 i.v. weekly; L-OHP 50 mg/m2; FA 500 mg/m2, 5-FU 1,500 mg/m2 [dose level 1] or 2,000 mg/m2 [dose level 2] i.v. over 24h weekly for 4 weeks followed by 1 week rest). Results: 49 pts have been enrolled, M/F 31/18, median age 62 years (39 - 78), median ECOG performance status 0 (0 - 2). 48 pts are assessable for safety and efficacy. In the phase I part dose limiting toxicities consisting of diarrhea gr 3 occurred in 1 (14%) out of 7 pts and in 3 (20%) out of 15 pts treated at dose level 1 (DL1) and 2 respectively. Consequently, DL2 using cetuximab together with L-OHP/5-FU/FA at their standard doses was considered as recommended dose (RD) for phase II and was expanded to 41 pts. Common gr 3/4 toxicities (pts ≥ 5%, multiple cycles at the RD): neutropenia 10%, mucositis 7%, gr 3 toxicity: diarrhea 24%, neurological 10%, skin 17%. Efficacy: 54% (95% CI 38 - 69%) confirmed remission including one CR was achieved in 41 pts at the RD and 5 (71%, 95% CI 29 - 96%) out of 7 pts at DL1 showed a PR. 3 PR pts at the RD underwent surgery for metastases. Median progression free survival time will be presented. Conclusion: The combination of cetuximab and FUFOX showed at the RD an acceptable safety profile and promising efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA Merck KgaA, sanofi-aventis Merck KgaA, sanofi-aventis Merck KgaA, sanofi-aventis