Cetuximab: new safety information available
- Medicines and Healthcare products Regulatory Agency
- 12 February 2014
- Therapeutic area:
importance of establishing wild type RAS (KRAS and NRAS) status before treatment of metastatic colorectal cancer
Article date: February 2014
Cetuximab (Erbitux) is a treatment for people with metastatic colorectal cancer.
New safety information has become available from a retrospective subset analysis of data from a randomised, multicentre phase II study (OPUS trial EMR 62202-0471) of cetuximab plus (oxaliplatin-containing) FOLFOX4 chemotherapy versus FOLFOX4 alone in people with previously untreated metastatic colorectal cancer. The OPUS trial included 337 people, 179 of whom had wild type KRAS exon 2 tumour status; incidence of additional RAS mutations (at NRAS exons 2, 3 and 4, and at KRAS exons 3 and 4) in this subset was 30•5%.
People with RAS mutations who were randomly assigned cetuximab plus FOLFOX4 had inferior survival, progression-free survival and objective response rates than did those assigned FOLFOX4 alone. Safety evaluations showed no new findings attributable to cetuximab when comparing wild type and mutated RAS populations: the inferior outcome was due to lack of efficacy in combination with the known toxicity profile as outlined in the product information.
Evidence of wild type RAS status at exons 2, 3, and 4 of KRAS and NRAS is required before initiating treatment with cetuximab alone or in combination with chemotherapy in metastatic colorectal cancer. Cetuximab combined with oxaliplatin-containing chemotherapy (eg, FOLFOX4) is now contraindicated in people with metastatic colorectal cancer who have mutant RAS (at exons 2, 3, and 4 of KRAS and NRAS) or unknown RAS status.
Advice for healthcare professionals:
- evidence of wild type RAS status (at exons 2, 3, and 4 of KRAS and NRAS) is required before initiating treatment with cetuximab alone or in combination with chemotherapy in metastatic colorectal cancer
- cetuximab combined with oxaliplatin-containing chemotherapy (eg, FOLFOX4) is contraindicated in all people with metastatic colorectal cancer who have mutant or unknown RAS status
- RAS mutation status should be determined by an experienced laboratory using a validated test method
- prescribing information for cetuximab in the treatment of people with squamous-cell carcinoma of the head and neck is not changed by the new information from this analysis
See letter sent to healthcare professionals in January 2014
See similar advice issued for panitumumab (Vectibix) in September 2013
Article citation: Drug Safety Update volume 7 issue 7, February 2014: A1.
Bokemeyer C, et al. J Clin Oncol 2009; 27: 663–71 ↩
Published: 12 February 2014
Therapeutic area: Cancer