Phase II trial of aflibercept with FOLFIRI as a second‐line treatment for Japanese patients with metastatic colorectal cancer

Aflibercept targets vascular endothelial growth factor. The present study involved assessing the efficacy, safety and pharmacokinetics of aflibercept plus 5‐fluorouracil/levofolinate/irinotecan (FOLFIRI) as a second‐line treatment for metastatic colorectal cancer (mCRC) in Japanese patients. Aflibercept (4 mg/kg) plus FOLFIRI was administered every 2 weeks in 62 patients with mCRC until disease progression, unacceptable toxicity or patient withdrawal. Tumors were imaged every 6 weeks. The primary endpoint was objective response rate (ORR); secondary endpoints were progression‐free survival, overall survival, safety, and pharmacokinetics of aflibercept, irinotecan and 5‐fluorouracil. A total of 60 patients were evaluated for ORR; 50 had received prior bevacizumab. The ORR was 8.3% (95% confidence interval [CI]: 1.3%‐15.3%), and the disease control rate (DCR) was 80.0% (69.9%‐90.1%). The median progression‐free survival was 5.42 months (4.14‐6.70 months) and the median overall survival was 15.59 months (11.20‐19.81 months). No treatment‐related deaths were observed, and no significant drug‐drug interactions were found. The most common treatment‐emergent adverse events were neutropenia and decreased appetite. Free aflibercept had a mean maximum concentration (coefficient of variation) of 73.2 μg/mL (15%), clearance of 0.805 L/d (22%) and volume of distribution of 6.2 L (18%); aflibercept bound with vascular endothelial growth factor had a clearance of 0.162 L/d (9%) (N = 62). Aflibercept did not significantly affect the pharmacokinetics of irinotecan or 5‐fluorouracil: The clearance was 11.1 L/h/m(2) (28%) for irinotecan and, at steady state, 72.6 L/h/m(2) (56%) for 5‐fluorouracil (N = 10). Adding aflibercept to FOLFIRI was shown to be beneficial and well‐tolerated in Japanese patients with mCRC. ClinicalTrials.gov Identifier: NCT01882868.