Erlotinib ( Tarceva ) is the first drug and the only EGFR-targeted treatment shown to prolong survival in a phase III trial ( PA3 ) when added to standard of care ( Gemcitabine ) for the treatment of patients with previously untreated advanced pancreatic cancer.
Tarceva was approved by the FDA in 2004 for the treatment of patients with locally advanced or metastatic non-small cell lung cancer ( NSCLC ) after failure of at least one prior chemotherapy regimen.
Pancreatic cancer is the fourth leading cause of all cancer deaths worldwide and is the tenth most frequently occurring cancer in Europe. In 2002, there were more than 78,000 new cases of pancreatic cancer diagnosed in Europe. Pancreatic cancer is difficult to treat, as it is often resistant to chemotherapy and radiotherapy, and tends to spread quickly to other parts of the body, leading to its high mortality and short life expectancy.
The PA3 study, a pivotal phase III multi-center, randomised, double-blind, placebo-controlled trial evaluated Erlotinib in 569 patients with locally advanced or metastatic pancreatic cancer.
The study demonstrated a 23.5 percent improvement in overall survival for patients receiving Erlotinib plus Gemcitabine compared to patients receiving Gemcitabine plus placebo ( hazard ratio = 0.81, p = 0.025 ).
Twenty-four percent of patients receiving Erlotinib plus Gemcitabine were alive after one year compared to 17 percent of patients receiving Gemcitabine plus placebo.
Median survival in the Erlotinib plus Gemcitabine arm was 6.4 months compared to 5.9 months in the Gemcitabine plus placebo arm.
Progression-free survival in the Erlotinib plus Gemcitabine arm also was significantly improved ( hazard ratio = 0.76, p = 0.003 ).
. The analysis of safety data did not reveal any unexpected safety signals beyond that seen in previous studies of Erlotinib in both monotherapy and combination settings.
Erlotinib is an investigational small molecule that targets the human epidermal growth factor receptor ( HER1 ) pathway.
HER1, also known as EGFR, is a key component of this signalling pathway, which plays a role in the formation and growth of numerous cancers.
Erlotinib blocks tumour cell growth by inhibiting the tyrosine kinase activity of the HER1 signalling pathway inside the cell.
Source: Roche, 2005