Bevacizumab

From Ganfyd

Jump to: navigation, search

Bevacizumab is a humanised recombinant monoclonal antibody against vascular endothelial growth factor (VEGF). VEGF-mediated angiogenesis is thought to sustain the growth of many cancers and this is the rationale behind targetting VEGF.

It is also efficacious in treating proliferative diabetic retinopathy[1] and wet macular degeneration by intra-ocular injection, which is cheaper than Ranibizumab (essentially bevacizumab with some antibody chain chopped off, and made by the same manufacturer). Up to two years, randomised controlled trials have shown no significant cardiovascular complications in intra-ocular administration [2] although this is a distinct long-term issue when it is given systemically.

Contents

Indication

  • Licensed for metastatic carcinoma of the colon or rectum.
  • Combination with interferon alfa-2a in renal cell cancer
  • Platinum resistant recurrent ovarian cancer
  • There has been use for intra-vitreal use of bevacizumab wet age-related macular degeneration but the drug is not licensed for this indication and there is no evidence that the license holder (Novarits) intends to sponsor the studies necessary for this to occur. Indeed, in 2012, Novartis started legal proceedings to challenge a primary care cluster's decision to allow bevacizumab to be used for ophthalmological indications instead of instead of ranibizumab.[3]

Independent evidence is however accumulating on safety[4] and efficacy in a number of intra-ocular indications.[5][6][7][8] It has a higher molecular weight than licensed alternatives (i.e. Ranibizumab) meaning it is theoretically less likely to cause systemic side-effects and, in intravitreal use, has a relatively long half-life of 5-10 days. The difference in properties may be important but this needs further study and could go either way in terms of net benefit.[9] Bevacizumab and ranibizumab use was not associated with increased risks of mortality, myocardial infarction, bleeding, or stroke compared with photodynamic therapy or pegaptanib.[10] Ranibizumab is not any safer with respect to vascular thrombotic events or death and may be safer with respect to severe intra-ocular inflammation than bevacizumab[11]. [2]. Combining the CATT results with the additional IVAN trial data suggests equivalent clinical effectiveness with a net tolerably of bevacizumab slightly less than ranibizumab for, at current prices, much greater cost effectiveness (the difference in price for is about 10-15 fold, ignoring the time and effort required to split the doses of bevacizumab).

Flag of the United Kingdom.png

As of 2012 the commissioning of this anti-VGEF agent in the NHS for ocular indications on resource effectiveness grounds[12] is under legal challenge.[3]

Negative indications

Flag of USA.png

The FDA began in late 2010 the procedure to withdraw it for breast cancer as the promise of an initial trial was followed by two subsequent trials with worse outcome[13]. The process of withdrawal was completed in November 2011

Possible indications

Any condition associated with tissue proliferation.

Contraindications

Side-effects

References

  1. Avery RL, Pearlman J, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ, Wendel R, Patel A. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology. 2006 Oct; 113(10):1695.e1-15.(Link to article – subscription may be required.)
  2. a b Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, Toth C, Redford M, Ferris FL. Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration: Two-Year Results. Ophthalmology. 2012 Apr 26.(Epub ahead of print) (Link to article – subscription may be required.)
  3. a b Torjesen I. Novartis takes legal action over trusts' advice to use bevacizumab for wet AMD. BMJ (Clinical research ed.). 2012; 344:e2959.(Epub)
  4. Schmucker C, Loke YK, Ehlken C, Agostini HT, Hansen LL, Antes G, Lelgemann M. Intravitreal bevacizumab (Avastin) versus ranibizumab (Lucentis) for the treatment of age-related macular degeneration: a safety review. The British journal of ophthalmology. 2010 Oct 22.(Epub ahead of print) (Link to article – subscription may be required.)
  5. Cheng CK, Peng CH, Chang CK, Hu CC, Chen LJ. ONE-YEAR OUTCOMES OF INTRAVITREAL BEVACIZUMAB (AVASTIN) THERAPY FOR POLYPOIDAL CHOROIDAL VASCULOPATHY. Retina (Philadelphia, Pa.). 2011 Feb 11.(Epub ahead of print) (Link to article – subscription may be required.)
  6. Shah NJ, Shah UN. Long-term effect of early intervention with single intravitreal injection of bevacizumab followed by panretinal and macular grid photocoagulation in central retinal vein occlusion (CRVO) with macular edema: A pilot study. Eye (London, England). 2011 Feb; 25(2):239-44.(Link to article – subscription may be required.)
  7. Hrisomalos FN, Maturi RK, Pata V. Long-term use of intravitreal bevacizumab (avastin) for the treatment of von hippel-lindau associated retinal hemangioblastomas. The open ophthalmology journal. 2010; 4:66-9.(Epub) (Link to article – subscription may be required.)
  8. The Intravitreal Use of Bevacizumab (Avastin) in AMD. The Royal College of Ophthalmologists accessed 1 Aug 2007
  9. Meyer CH, Holz FG. Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab. Eye (London, England). 2011 Apr 1.(Epub ahead of print) (Link to article – subscription may be required.)
  10. Curtis LH, Hammill BG, Schulman KA, Cousins SW. Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age-related macular degeneration. Archives of ophthalmology. 2010 Oct; 128(10):1273-9.(Link to article – subscription may be required.)
  11. Carneiro AM, Barthelmes D, Falcão MS, Mendonça LS, Fonseca SL, Gonçalves RM, Faria-Correia F, Falcão-Reis FM. Arterial thromboembolic events in patients with exudative age-related macular degeneration treated with intravitreal bevacizumab or ranibizumab. Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift für Augenheilkunde. 2011; 225(4):211-21.(Link to article – subscription may be required.)
  12. Mitchell P, Annemans L, White R, Gallagher M, Thomas S. Cost effectiveness of treatments for wet age-related macular degeneration. PharmacoEconomics. 2011 Feb 1; 29(2):107-31.(Link to article – subscription may be required.)
  13. Regulatory Decision to Withdraw Avastin (bevacizumab) Firstline Metastatic Breast Cancer Indication
  14. Mintz-Hittner HA, Kennedy KA, Chuang AZ. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. The New England journal of medicine. 2011 Feb 17; 364(7):603-15.(Link to article – subscription may be required.)