Aflibercept

Aflibercept is a recombinantly produced, anti-angiogenetic fusion protein. The substance consists of the binding sites of both receptors of the vascular endothelial growth factor VEGF-R1 and VEGF-R2. Aflibercept is therefore able to intercept not only the VEGF-A ligand, but also VEGF-B and PlGF (placental growth factor). All three growth factors play an important role in tumour angiogenesis. This triple target of Aflibercept allows for a particularly effective anti-angiogenic blockade.

Aflibercept is approved in Germany under the name Eylea®for five indications: neovascular age-related macular degeneration (wet AMD), visual impairment due to diabetic macular edema or macular edema resulting from retinal vein occlusion (branch or central retinal vein occlusion) and for the treatment of visual impairment due to myopic choroidal neovascularization. With around 20 million vials sold since its launch, Aflibercept is the global market leader in anti-VEGF treatment. In 2015, the product received EU approval for the indication myopic choroidal neovascularization (mCNV).

Aflibercept continues to be used as Zaltrap® in the treatment of metastatic colorectal cancer. Aflibercept is intended to be used in this indication in combination with folinic acid (leucovorin), fluoruracil (5-FU) and irinotecan (FOLFIRI) in adults. The cancer should be resistant to oxaliplatin or continue to progress after treatment with oxaliplatin.

The European Commission has granted marketing approval for Aflibercept (Zaltrap®) in combination with folinic acid, fluoruracil and irinotecan (FOLFIRI chemotherapy). The FOLFIRI combination was approved for the treatment of patients with metastatic colorectal cancer (mCRC) who did not respond to treatment with an oxaliplatin-containing regimen.

(Zaltrap®⁾: The most common side effects of Zaltrap® are: leukopenia, thrombocytopenia, diarrhea, neutropenia, proteinuria, pearl, stomatitis; fatigue, hypertension, weight loss, reduced appetite, epistaxis, abdominal pain, dysphonia, elevated serum creatinine levels.

In combination with folinic acid, fluoruracil and irinotecan (FOLFIRI chemotherapy), palmoplantar erythrodysesthesia syndrome and frequent hyperpigmentation of the skin are very often found. Occasionally, disturbed wound healing and osteonecrosis of the jawbone occur.

ADR (Eylea®): The most common side effects of Eylea® are: conjunctival hemorrhage; eye pain; cataracts; floaters; increased intraocular pressure; vitreous detachment; serious side effects include eye infections (endophthalmitis) and retinal detachment.

Contra (Zaltrap®): female and male reproduction (up to 6 months after therapy), pregnancy, lactation

Eylea®; Zaltrap®

1. Auvray M et al (2020) Efficacy and Safety of Aflibercept in Combination With Chemotherapy Beyond Second-Line Therapy in Metastatic Colorectal Carcinoma Patients: To AGEO Multicenter Study. Clin Colorectal Cancer 19:39-47.
2. Barmas-Alamdari D et al.(2019) Intravitreal Ziv- Aflibercept: A Comprehensive Review. Semin Ophthalmol 34:420-435.
3. Cai S et al (2017) Aflibercept, bevacizumab or ranibizumab for diabetic macular oedema: recent clinically relevant findings from DRCR.net Protocol T. Curr Opin Ophthalmol 28:636-643.
4. Lopez A et al (2019) Targeting Angiogenesis in Colorectal Carcinoma. Drugs 79:63-74.