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

<jats:p>Aflibercept targets vascular endothelial growth factor. The present study involved assessing the efficacy, safety and pharmacokinetics of aflibercept plus 5‐fluorouracil/levofolinate/irinotecan (<jats:styled-content style="fixed-case">FOLFIRI</jats:styled-content>) as a second‐line treatment for metastatic colorectal cancer (<jats:styled-content style="fixed-case">mCRC</jats:styled-content>) in Japanese patients. Aflibercept (4 mg/kg) plus <jats:styled-content style="fixed-case">FOLFIRI</jats:styled-content> was administered every 2 weeks in 62 patients with <jats:styled-content style="fixed-case">mCRC</jats:styled-content> until disease progression, unacceptable toxicity or patient withdrawal. Tumors were imaged every 6 weeks. The primary endpoint was objective response rate (<jats:styled-content style="fixed-case">ORR</jats:styled-content>); 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 <jats:styled-content style="fixed-case">ORR</jats:styled-content>; 50 had received prior bevacizumab. The <jats:styled-content style="fixed-case">ORR</jats:styled-content> was 8.3% (95% confidence interval [CI]: 1.3%‐15.3%), and the disease control rate (<jats:styled-content style="fixed-case">DCR</jats:styled-content>) 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/<jats:styled-content style="fixed-case">mL</jats:styled-content> (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<jats:sup>2</jats:sup> (28%) for irinotecan and, at steady state, 72.6 L/h/m<jats:sup>2</jats:sup> (56%) for 5‐fluorouracil (N = 10). Adding aflibercept to <jats:styled-content style="fixed-case">FOLFIRI</jats:styled-content> was shown to be beneficial and well‐tolerated in Japanese patients with <jats:styled-content style="fixed-case">mCRC</jats:styled-content>. ClinicalTrials.gov Identifier: <jats:styled-content style="fixed-case">NCT</jats:styled-content>01882868.</jats:p>