Erlotinib in addition to gemcitabine significantly improves overall survival compared to gemcitabine alone in advanced pancreatic cancer (median overall survival 6.24 vs 5.91 months respectively). However, combined therapy has not become standard of care due to the modest absolute benefit. In NSCLC, the optimal efficacy of erlotinib is not in combination with first-line cytotoxic chemotherapy for advanced disease, but as a single agent after cytoxic chemotherapy. Preclinical and clinical data suggest that erlotinib will have activity as a single agent in advanced pancreatic cancer. The presence of an erlotinib-induced rash is associated with improved survival in phase II and III trials of diverse tumor types (reviewed by Perez-Soler et al.), and is associated with higher steady state concentrations of erlotinib.~This phase II trial aims to determine the safety and efficacy of erlotinib in patients with advanced pancreatic cancer who have previously been treated with up to one prior line of gemcitabine based chemotherapy for advanced disease. In addition, we will evaluate the feasibility and activity of dose escalation of erlotinib in patients who do not develop a rash. Clinical outcome will be correlated to EGFR status based on immunohistochemistry and gene amplification status as well as Kras mutations from archival tumor tissue.
This is an open-label, multi-center phase II study of erlotinib in patients with metastatic or locally advanced, unresectable pancreatic cancer who have received up to one line of gemcitabine based chemotherapy.