Herceptin filed in US for HER2-positive stomach cancer
This article was originally published in Scrip
Genentech (Roche) has filed for supplemental US FDA approval for its HER2-targeted drug Herceptin (trastuzumab) to treat advanced, HER2-positive gastric cancer, including gastroesophageal junction cancer.
"This application reflects our commitment to developing more personalised medicines for people with cancer. By using diagnostics to help identify the right patients for our medicines, it is our hope that Herceptin used with chemotherapy will become the first targeted option for advanced HER2-positive stomach cancer," said Dr Hal Barron, Roche's chief medical officer.
In January, Herceptin was approved for the same indication in the EU. The CHMP in December said Herceptin could be used as first-line treatment for about 16% of patients with HER2-positive metastatic gastric cancer (scripnews.com 21 December 2009). Roche's subsidiary Chugai also filed for the Japanese approval of Herceptin for the treatment of HER2-positive advanced or recurrent gastric cancer in March.
The US filing and EU approval are both based on the ToGA trial, which tested Herceptin in combination with chemotherapy in patients with HER2-positive gastric cancer, compared with standard chemotherapy alone. Median overall survival improved from 11.1 to 13.8 months.
The survival difference was even larger for patients who had higher levels of HER2 protein on their cancer cells. An exploratory analysis conducted by the study's lead investigator, Dr Eric Van Cutsem of the University Hospital Gasthuisberg in Belgium, showed that for these patients, median survival was extended from 11.8 to 16 months. The CHMP had based its EU recommendation for approval on these patients.
Herceptin first generated excitement in breast cancer when it improved overall survival in advanced HER2-positive disease by about five months. It is one of the first successful examples of "personalised medicine" in oncology, showing that clinical outcomes can be improved if the molecular drivers of a particular subset of cancer are identified and then specifically targeted.
If approved in the US, Herceptin would become the first "targeted" anticancer to be used to treat gastric cancer, where chemotherapy is still the standard of care. Annual incidence in the US is more than 20,000, and there are more than 10,000 deaths each year. Gastric cancer has a particularly high incidence in Japan and Korea.
Gastric cancer is associated with a poor prognosis, with five-year survival under 30% in Europe and the US. This is because the majority of patients present with late-stage disease.
Roche's anti-VEGF monoclonal antibody drug Avastin (bevacizumab), recently failed its only Phase III trial in gastric cancer.
GlaxoSmithKline is testing its rival to Herceptin, the HER2 and EGFR-targeted Tykerb (lapatinib), in a Phase III Asian trial in second-line HER2-positive gastric cancer.
Lilly/BMS/Merck KGaA are testing the benefit of the EGFR-targeted monoclonal antibody drug, Erbitux (cetuximab), as a first-line treatment in combination with standard chemotherapy.