Pertuzumab

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Pertuzumab ?
Pertuzumab-HER2 complex 1S78.png
The structure of HER2 and pertuzumab
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target HER2
Clinical data
Trade names Perjeta; Omnitarg
Licence data US FDA:link
Pregnancy cat.
Legal status
Routes Intravenous
Identifiers
CAS number 380610-27-5 N
ATC code L01XC13
UNII K16AIQ8CTM YesY
KEGG D05446 YesY
ChEMBL CHEMBL2007641 N
Chemical data
Formula ?
 N (what is this?)  (verify)

Pertuzumab (also called 2C4, trade name Perjeta) is a monoclonal antibody marketed by Genentech for the treatment of HER2-positive breast cancer, in combination with trastuzumab and docetaxel.[1] The first of its class in a line of agents called "HER dimerization inhibitors". By binding to HER2, it inhibits the dimerization of HER2 with other HER receptors, which is hypothesized to result in slowed tumor growth.[2] Pertuzumab received US FDA approval for the treatment of HER2-positive metastatic breast cancer on June 8, 2012.[3] Pertuzumab was developed at Genentech and is now owned by Roche which acquired Genentech in 2009.

Clinical trials[edit]

Early clinical trials of pertuzumab in prostate, breast, and ovarian cancers met with limited success.[4]

The dosage of pertuzumab used in the pivotal phase III CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) trial was as follows: IV 840 mg loading dose followed by IV 420 mg every three weeks.[5]

The pharmacokinetics of intravenous pertuzumab appear to be unaffected by age and no drug-drug interaction has been reported with docetaxel. The pharmacokinetics and pharmacodynamics of pertuzumab were summarized in a Feb 2012 review by Gillian Keating.[5]

The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects in the randomized, double-blind, multinational, phase III CLEOPATRA trial.[5]

Intravenous pertuzumab is currently being evaluated in patients with breast cancer in the following trials: MARIANNE (advanced breast cancer), NEOSPHERE (early breast cancer), TRYPHAENA (HER2-positive stage II/III breast cancer) and APHINITY (HER2-positive nonmetastatic breast cancer).[5]

References[edit]

  1. ^ http://www.gene.com/download/pdf/perjeta_prescribing.pdf
  2. ^ de Bono, Johann S.; Bellmunt, J; Attard, G; Droz, JP; Miller, K; Flechon, A; Sternberg, C; Parker, C et al. (20 January 2007). "Open-Label Phase II Study Evaluating the Efficacy and Safety of Two Doses of Pertuzumab in Castrate Chemotherapy-Naive Patients With Hormone-Refractory Prostate Cancer". Journal of Clinical Oncology 25 (3): 257–262. doi:10.1200/JCO.2006.07.0888. PMID 17235043. 
  3. ^ "FDA Approves Perjeta (Pertuzumab) for People With HER2-Positive Metastatic Breast Cancer" (Press release). Genentech. Retrieved 2012-06-09. 
  4. ^ Genentech press release - May 15, 2005
  5. ^ a b c d Keating GM. Pertuzumab: in the first-line treatment of HER2-positive metastatic breast cancer. Drugs 2012 Feb 12; 72 (3): 353-60.Link text

External links[edit]

10.1056/NEJMoa1113216