cetuximab (Erbitux) and panitumumab (Vectibix)

cetuximab (Erbitux) and panitumumab (Vectibix)
Class Labeling Changes to anti-EGFR monoclonal antibodies, cetuximab (Erbitux) and panitumumab (Vectibix): KRAS Mutations

On July 17, 2009, changes were made to the product labels of cetuximab (ErbituxImClone Systems, Branchburg, NJ) and panitumumab (Vectibix Amgen, Thousand Oaks, CA). Retrospective subset analyses of trials in patients with colorectal cancers having KRAS mutations noted a lack of benefit associated with these monoclonal antibodies. The percentage of study populations for which KRAS status was assessed ranged from 23% to 92%.

Labeling changes have been implemented in the INDICATIONS AND USAGE, CLINICAL PHARMACOLOGY, and CLINICAL STUDIES sections of both cetuximab and panitumumab product labels.

The following new information has been added to the cetuximab label:

INDICATIONS AND USAGE
1.2 Colorectal Cancer:

Retrospective subset analyses of metastatic or advanced colorectal cancer trials have not shown a treatment benefit for Erbitux in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Erbitux is not recommended for the treatment of colorectal cancer with these mutations [see Clinical Studies (14.2) and Clinical Pharmacology (12.1)].

The following new information has been added to the panitumumab label:

INDICATIONS AND USAGE
Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for Vectibix in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Vectibix is not recommended for the treatment of colorectal cancer with these mutations [see Clinical Studies (14) and Clinical Pharmacology (12.1)].

The following new information has been added to the product labels for both cetuximab and panitumumab:

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Signal transduction through the EGFR results in activation of wild-type KRAS protein. However, in cells with activating KRAS somatic mutations, the mutant KRAS protein is continuously active and appears independent of EGFR regulation.

CLINICAL STUDIES
14 Vectibix label

14.2 Erbitux label

Lack of Efficacy of Anti-EGFR Monoclonal Antibodies in Patients with mCRC Containing KRAS Mutations
Retrospective analyses as presented in Table 5 (Erbitux label), Table 2 (Vectibix label) across seven randomized clinical trials suggest that anti-EGFR monoclonal antibodies are not effective for the treatment of patients with mCRC containing KRAS mutations. In these trials, patients received standard of care (i.e., BSC or chemotherapy) and were randomized to receive either an anti-EGFR antibody (cetuximab or panitumumab) or no additional therapy. In all studies, investigational tests were used to detect KRAS mutations in codon 12 or 13. The percentage of study populations for which KRAS status was assessed ranged from 23% to 92%. [See Clinical Pharmacology (12.1).]

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cetuximab (Erbitux) and panitumumab (Vectibix)