Panitumumab

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Panitumumab
Mass / length primary structure 144.3  kDa
Identifier
External IDs
Drug information
ATC code L01 XC08
DrugBank DB01269
Drug class Monoclonal antibody

Panitumumab (trade name Vectibix ; manufacturer Amgen ) is a human monoclonal antibody from the group of immunoglobulins IgG 2κ . It binds to the receptor of the proliferation factor EGF ( Epidermal Growth Factor ), a protein that plays an important role in the signal transduction of cells . When panitumumab binds to the EGF receptor , the subsequent signaling cascade is blocked and cell proliferation is inhibited. Compared to chimeric antibodies (e.g. cetuximab , which is also directed against the EGFR) and humanized antibodies, panitumumab does not contain any foreign protein that could be recognized as foreign protein by the body's immune system.

Indication and development

Panitumumab is approved as monotherapy for the treatment of metastatic, EGFR-expressing colorectal cancer with non-mutated (wild-type) KRAS gene in patients who have failed chemotherapy regimens containing fluoropyrimidine , oxaliplatin and irinotecan .

The goal of developing a complete human monoclonal antibody was to achieve an effective and targeted therapy with a reduced risk of immune reactions. Panitumumab was developed by the biotechnology company Abgenix using so-called Xeno-Mouse technology in 2002. Since the takeover of Abgenix in 2006, the patent rights have been owned by the biotechnology company Amgen . The peculiarity of this antibody is that it has no xenogenic (that is, non-species) components - i.e. it is completely human - and therefore has a low immunogenicity .

For the first time, the influence of the KRAS gene (mutated versus non-mutated) on the therapeutic success of EGFR antibodies was demonstrated in the panitumumab approval study . The data made it clear that only patients (approx. 60%) benefited from panitumumab therapy whose tumors had a non-mutated KRAS gene (wild type). The KRAS protein is located in the EGFR signal cascade downstream of the EGF receptor. If this gene is mutated, it results in a functionally changed protein (constitutively active), i.e. the signal transmission is permanently active, even if it has been blocked above at the receptor. Tumors with a mutated KRAS gene therefore do not respond to anti-EGFR therapy as with panitumumab. In the meantime, KRAS has been established as an oncogene with predictive significance in metastatic colorectal cancer .

Admission

Panitumumab was approved in the United States in September 2006. It was approved in the European Union in December 2007 as a monotherapy for the treatment of metastatic, EGFR-expressing colorectal cancer with non-mutated (wild-type) KRAS gene in patients who have failed chemotherapy regimens containing fluoropyrimidine , oxaliplatin and irinotecan .

In September 2009, the results of two large phase III studies (which for the first time included prospective KRAS data) made the effectiveness of Vectibix ® clear, also in combination with chemotherapy (1st and 2nd line therapy). In April 2010, the EMA therefore submitted an application to expand the indication for the combination with chemotherapy.

Side effects and restrictions on use

The most common undesirable effects reported were skin reactions, gastrointestinal disorders such as diarrhea, nausea, vomiting and constipation, as well as abdominal pain, fatigue and metabolic and nutritional disorders. Serious side effects such as corneal inflammation of the eye ( keratitis ) occurred in rare cases, but more often serious inflammatory diseases of the skin or connective tissue ( fasciitis ). In colorectal cancer with a mutated KRAS gene, panitumumab is not effective and, in combination with certain other chemotherapeutic agents ( FOLFOX ), even has an adverse effect, which is why determining the KRAS status is important.

See also

Individual evidence

  1. ↑ A. Jakobovits, inter alia: From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice. In: Nat. Biotechnol. 25 (10), 2007. pp. 1134-1143. PMID 17921999
  2. ↑ Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG: Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy . In: Critical Reviews in Oncology Hematology . 38, No. 1, April 2001, pp. 17-23. PMID 11255078 . Retrieved August 4, 2010.
  3. ↑ Specialist information Vectibix June 2012 (PDF; 209 kB), accessed on July 17, 2012.
  4. ↑ a b Amado RG, Wolf M, Peeters M, among others: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer . In: Journal of Clinical Oncology  : Official Journal of the American Society of Clinical Oncology . 26, No. 10, April 2008, pp. 1626-1634. PMID 18316791 . Retrieved August 4, 2010.
  5. ↑ a b Public Assessment Report (EPAR) of the European Medicines Agency (EMA) on: Vectibix .
  6. ↑ Peeters M et al. ECCO / ESMO 2009: Abstract 14LBA.
  7. ↑ Douillard JY et al. ECCO / ESMO 2009: Abstract 10LBA.
  8. ↑ Rote-Hand-Brief from the Drugs Commission of the German Medical Association (AkdÄ)
  9. ↑ Rote-Hand-Brief from Amgen on July 10, 2012 (PDF; 449 kB) Retrieved on July 17, 2012 .
  10. ↑ Rote-Hand-Brief from Amgen on November 23, 2011. (PDF; 1.6 MB) Retrieved on August 24, 2011 .
  11. ↑ Rote-Hand-Brief from Amgen on August 13, 2013. (PDF; 561 kB) Accessed on August 13, 2013 .

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