Bevacizumab or Cetuximab in Combination with Chemotherapy for mCRC

Chicago—Patients with metastatic colorectal cancer (mCRC) had no difference in overall survival or progression-free survival if they received bevacizumab plus chemotherapy or cetuximab plus chemotherapy for first-line treatment, according to a randomized, phase 3 trial. They were given FOLFOX (oxaliplatin/5-fluorouracil/leucovorin) or FOLFORI (irinotecan/5-fluorouracil/leucovorin) chemotherapy.

The median overall survival was 29.9 months in the cetuximab group and 29 months in the bevacizumab group (hazard ratio [HR], 0.925; P=.34). The median progression-free survival was 10.4 months in the cetuximab group and 10.8 months in the bevacizumab group (HR, 1.04; P=.55).

Alan P. Venook, MD, the study’s lead author, presented the results during a plenary session at ASCO meeting. The study was funded by the National Cancer Institute. The Alliance for Clinical Trials in Oncology and the Southwest Oncology Group helped conduct the trial.

Of the patients, 73% received FOLFOX chemotherapy and 27% received FOLFORI chemotherapy. For patients who received FOLFOX chemotherapy, the median overall survival was 30.1 months in the cetuximab group and 26.9 months in the bevacizumab group (HR, 0.9; P=.09). For patients who received FOLFORI chemotherapy, the median overall survival was 28.9 months in the cetuximab group and 33.4 months in the bevacizumab group (HR, 1.2; P=.28). Dr. Venook said, “we cannot draw any conclusions” for the FOLFORI-treated patients because it only included 302 patients.

Furthermore, 11% of patients (n=124) were considered disease-free after surgery and chemotherapy. Among those patients, the median overall survival was 66.3 months. “There is a subset of patients with [mCRC] who will do exceedingly well, and we need to take that message home with us,” Dr. Venook said.

Dr. Venook added that the regimens were “very well-tolerated.” Grade 3 toxicities were found in approximately half of patients, and 10 patients died because of toxicities. Hypertension and gastrointestinal events were more common in patients who received bevacizumab, while rash and diarrhea were more common with cetuximab. Fewer than one-third of patients discontinued therapy due to progressive disease.

Bevacizumab, a vascular endothelial growth factor-specific angiogenesis inhibitor, is approved to treat mCRC with 5-fluorouracil-based chemotherapy for first- or second-line therapy. Cetuximab, an epidermal growth factor receptor antagonist, is approved to treat KRAS, wild-type mCRC in combination with FOLFORI for first-line treatment.

This was the eleventh interim analysis of the study, which was conceived in 2004 and undertaken to evaluate if there was an optimal first-line treatment for this patient population. Dr. Venook said FOLFOX and FOLFORI are similar in efficacy but have different toxicities in mCRC. At that time, the overall survival associated with the disease was 20 to 22 months. Although new drugs have been approved in the past 10 years, Dr. Venook said the best first-line treatment is still unknown.

Patients were eligible if they had untreated mCRC whose tumors were KRAS wild-type at codons 12 and 13. They could have adjuvant therapy within 12 months of study enrollment and had to have an Eastern Cooperative Oncology Group status score of 0 or 1 and preserved organ function.

After 3 years of accrual, the study was amended because of advances in the treatment of the disease and was closed to accrual. In the final design, patients were assigned to chemotherapy with FOLFOX or FOLFORI at the discretion of their physician and were randomized to receive cetuximab or bevacizumab. The data was released on January 29, 2014.

The study enrolled 1137 patients. At baseline, the median age was 59 years, 61.3% of patients were male, 28% had their primary tumors in place, and 84.4% were treated with palliative intent.

Dr. Venook said data on response rates, duration of therapy and dose intensity, an analysis of special subsets of patients, and details on second and later treatments would be presented at a later date.