Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNING AND PRECAUTIONS
Increased Tumor Progression, Increased Mortality, or Lack of Benefit in Patients with RAS-Mutant mCRC
- Vectibix is not indicated for the treatment of patients with colorectal cancer that harbor somatic mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as “RAS” [see Indications and Usage (1.1), Dosage and Administration (2.1), Clinical Pharmacology (12.1) and Clinical Studies (14)].
- Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab).
- Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents [see Indications and Usage (1.1), and Clinical Pharmacology (12.1)].
- Additionally, in Study 3, 272 patients with RAS-mutant mCRC tumors received Vectibix in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix and FOLFOX versus FOLFOX alone [see Indications and Usage (1.1)].
WARNINGS AND PRECAUTIONS
Dermatologic and Soft Tissue Toxicity
- …It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (eg, Stevens Johnson syndrome or toxic epidermal necrolysis)…
Skin and subcutaneous tissue disorders:
- … life threatening and fatal bullous mucocutaneous disease
WARNINGS AND PRECAUTIONS
- Monitor patients who develop dermatologic toxicities while receiving Vectibix for the development of inflammatory or infectious sequelae…
Increased Mortality or Toxicity with Vectibix in Combination with Chemotherapy
- Vectibix is not indicated for use in combination with chemotherapy…
Pulmonary Fibrosis/Interstitial Lung Disease (ILD)
- Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix. Patients with a history or evidence of interstitial pneumonitis, pulmonary fibrosis, were excluded from most clinical trials…
- As monotherapy: The incidence of binding antibodies (excluding pre-existing and transient positive patients) was 0.4% (3/717), as detected by the acid dissociation ELISA, and 3.8% (27/717) as detected by the Biacore assay…
- In combination with irinotecan- or oxaliplatin-based chemotherapy: The incidence of binding antibodies (excluding pre-existing positive patients) was 1% (11/1124) as detected by the acid dissociation ELISA and 0.8% (9/1123) as detected by the Biacore assay…