Genentech and OSI Pharmaceuticals are telling healthcare professionals that cases of liver damage, including fatalities, have been reported in patients taking the cancer blockbuster Tarceva.
Specifically, the firms have notified doctors, via the US Food and Drug Administration’s website regulators, of data from a pharmacokinetic study in patients with advanced solid tumours and moderate hepatic impairment. In this study, ten of the 15 patients died on treatment or within 30 days of the last dose of Tarceva (erlotinib).
Although eight of these patients died from progressive disease, one died from hepatorenal syndrome and another died from rapidly progressing liver failure. Six out of the 10 patients who died had baseline total bilirubin three times greater than upper limit of normal or Child-Pugh A, B and C, suggesting severe, rather than moderate, hepatic impairment.
Genentech and OSI said that this highlighted “the limitations of utilising the Child-Pugh criteria in an oncology patient population. All patients had hepatic impairment due to advanced cancer with liver involvement such as hepatocellular carcinoma, cholangiocarcinoma, or liver metastases.
As a result of the findings, the firms say that patients with hepatic impairment “should be monitored closely during therapy with Tarceva, and dosing should be interrupted or discontinued if changes in liver function are severe”. Previously prescribing information for the drug included a ‘precaution’ about liver damage including fatalities. This language has been updated moved to the ‘warnings’ section of the label.
Tarceva is a big earner for Genentech and Roche, which owns a majority stake in the US biotechnology giant and has had an $89 per share offer for the remaining shares turned down. First-half sales of Tarceva, which is approved for monotherapy of locally advanced or metastatic non-small-cell lung cancer and in combination with gemcitabine for first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer, grew 28% to 587 million francs.
