Aflibercept plus FOLFIRI in Asian patients with pretreated metastatic colorectal cancer: a randomized Phase III study.

AIM To investigate whether the benefit of combining aflibercept with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) chemotherapy could be confirmed in patients from the Asia-Pacific region (ClinicalTrials.gov: NCT01661270). Patients & methods: Asian patients with oxaliplatin-pretreated metastatic colorectal cancer were randomized to receive aflibercept or placebo, followed by FOLFIRI. The primary end point was progression-free survival. RESULTS The intention-to-treat population comprised 332 patients. A clinical supply misallocation resulted in 198/332 (60%) patients receiving at least one cycle of misallocated treatment. Nevertheless, the addition of aflibercept to FOLFIRI was shown to improve progression-free survival (hazard ratio: 0.629; 95% CI: 0.488-0.812). Adverse events were in line with expectations. CONCLUSION The beneficial treatment effect associated with the addition of aflibercept to FOLFIRI was confirmed in Asian patients with pretreated metastatic colorectal cancer.

[1]  O. Clark,et al.  Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis , 2016, BMC Cancer.

[2]  B. Konda,et al.  Anti-angiogenic agents in metastatic colorectal cancer. , 2015, World journal of gastrointestinal oncology.

[3]  N. Pavlakis,et al.  The role of biological therapy in metastatic colorectal cancer after first-line treatment: a meta-analysis of randomised trials , 2014, British Journal of Cancer.

[4]  E. Van Cutsem,et al.  Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. , 2014, European journal of cancer.

[5]  A. Ohtsu,et al.  A phase I study of intravenous aflibercept with FOLFIRI in Japanese patients with previously treated metastatic colorectal cancer , 2012, Investigational New Drugs.

[6]  E. Van Cutsem,et al.  Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  G. Yancopoulos,et al.  Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab , 2012, Angiogenesis.

[8]  K. Chìn,et al.  Grade 3/4 neutropenia is a limiting factor in second-line FOLFIRI following FOLFOX4 failure in elderly patients with metastatic colorectal cancer. , 2011, Oncology letters.

[9]  Andreas Teufel,et al.  Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer , 2004, BMC Cancer.

[10]  M. van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors , 2000, Journal of the National Cancer Institute.