Ann: Sirtex Completes SIRFLOX Patient Recruitment, page-12

re: Ann: Sirtex Completes SIRFLOX Patient Rec... If their SIRFLOX trial is positive, they will no doubt (as most companies in this position do) submit the data to the FDA as a supplement to their existing PMA, with the intent of updating the labelling. The updated indication would likely be that SS are indicated in combination with FOLFOX chemotherapy as a first line treatment in patients with liver metastases from primary colorectal cancer.

The above notwithstanding, there are many examples of broad commercial uptake in which an agent is used in contravention to its approved FDA indication. In the therapeutic area of colorectal cancer, a prime example is Avastin (Roche). Avastin was approved in the US in 2004 in combination with an out moded irinotecan regimen known as IFL for the treatment of chemotherapy naive (ie first line) patients with advanced colorectal cancer. Upon US marketing launch in ~2005 Avastin was used almost exclusively in chemotherapy naive patients in combination with the oxaliplatin regimen known as FOLFOX (which constituted off label use), not with the FDA approved IFL. Furthermore, it was universally reimbursed for this off label use, with US sales in the order of $1B in its first year on market.

Please indicate what evidence you have of FOLFOX being overtaken by biologic drugs. In colorectal cancer, biologic drugs are rarely given alone but instead are almost univerally given in combination with a backbone chemotherapy. Usually FOLFOX or FOLFIRI. Biologic agents alone, without chemotherapy, are almost useless.