Erbitux: genotox, carcinogenicity and repro: done or skipped?

“the applicant decided to perform a partial genotoxicity study using in vitro and in vivo assays in terms of an AMES test and a rat micronucleus test. No genotoxic potential of Cetuximab was observed.”

“Based on the life-expectancy in the intended therapeutic indication, no long-term carcinogenisity studies are required80.”

“While no fetal malformations occurred in offspring, there was an increased incidence of embryolethality and abortions at doses approximately 1 to 4 times the recommended dose of ERBITUX based on BSA.”

“In conclusion, there were no indications of an effect of cetuximab on the cardiovascular and respiratory system.”

“In vitro genotoxicity investigations using Salmonella typhimurium and Escherichia coli as test systems with and without addition of liver S9 mix as external metabolising system yielded no indications of a mutagenic potential of Cetuximab.”

“the applicant decided to perform a partial genotoxicity study using in vitro and in vivo assays in terms of an AMES test and a rat micronucleus test.”

“Furthermore, in an in vivo cytogenetic assay performed as a micronucleus test in male Wistar rats, cetuximab was not genotoxic. The results of the micronucleus test are considered of limited value due to the lack of immunoreactivity of Cetuximab with tissues from rats”

“No standard carcinogenicity studies were performed with cetuximab as these are generally considered inappropriate for biotechnology-derived products79.”

“Based on the life-expectancy in the intended therapeutic indication, no long-term carcinogenisity studies are required80.”

“Electrocardiography, determination of heart rate and blood pressure (pre-dose, week 4, 13, 26 and 39, 1 h after infusion) revealed no findings related to treatment with cetuximab.”