OSI Pharmaceuticals Inc, Genentech Inc and Roche announced that results from a randomized phase III clinical study of the investigational drug Tarceva (erlotinib HCl), in combination with gemcitabine chemotherapy met its primary endpoint of improving survival.

According to a Genentech release, the international study demonstrated a statistically significant 23.5 per cent improvement in overall survival for patients with locally advanced or metastatic pancreatic cancer when compared to patients receiving gemcitabine plus placebo. A hazard ratio of 0.81 and a p-value of 0.025 were observed (a hazard ratio of less than one indicates a reduction in the risk of death and a p-value of less than 0.05 indicates statistical significance). Median and one-year survival in the Tarceva plus gemcitabine arm were 6.4 months and 25.6 per cent respectively compared to 5.9 months and 19.7 per cent in the gemcitabine plus placebo arm.

A statistically significant improvement in progression-free survival was also demonstrated, although no difference in tumour response was observed. A preliminary analysis of the safety data did not reveal any unexpected safety signal beyond that seen in prior use of Tarceva in both monotherapy and combination settings. As expected, rash and diarrhoea were the principal Tarceva related side effects seen in the study.

Malcolm Moore, study chair and medical oncologist at Princess Margaret Hospital and chair of the Gastrointestinal Disease Site, NCIC Clinical Trials Group stated, "Pancreatic cancer is widely recognized as a difficult disease to treat and new therapeutic regimens are desperately needed. These results also demonstrate that the HER1/EGFR signalling pathway is an important target in pancreatic cancer, and offer hope that further progress can be made."

"These data are important in that they open the door to a completely new approach in the treatment of pancreatic cancer, a disease in which currently only 20 per cent of patients survive one year after diagnosis," Hal Barron, Genentech's senior vice president, development and chief medical officer said adding, "We will work closely with our collaborators to continue to understand these data, as well as determine additional clinical studies to optimize the potential use of Tarceva in this disease setting. The alliance will discuss these data with the FDA and other regulatory agencies to determine the next steps for Tarceva in pancreatic cancer."

In July 2004, OSI completed the submission of a New Drug Application (NDA) with the FDA for Tarceva, as a monotherapy for the treatment of patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one standard chemotherapy regimen.

This was a multi-centre, randomized, double-blind, placebo-controlled Phase III study evaluating Tarceva at 100 mg/day or 150 mg/day in patients with locally advanced or metastatic pancreatic cancer. The study randomized patients to receive either gemcitabine plus concurrent Tarceva or gemcitabine plus placebo. A total of 569 patients were randomized in the study, 521 patients in the group who received 100 mg/day of Tarceva or placebo, and 48 patients in the group who received 150 mg/day of Tarceva or placebo.

Tarceva is designed to block tumour cell growth by inhibiting the tyrosine kinase activity of the HER1/EGFR receptor thereby blocking the HER1/EGFR signalling pathway inside the cell. Tarceva is currently being evaluated in an extensive clinical development program by a global alliance among OSI Pharmaceuticals, Genentech, and Roche.

Results from the study will be submitted for presentation at an appropriate peer-reviewed oncology meeting in the near future.