Description Tarceva® (erlotinib) is a small molecule designed to target the human epidermal growth factor receptor (HER1) pathway, also known as epidermal growth factor receptor (EGFR), which is critical to cell growth in many cancers. HER1/EGFR is a key component of the HER signaling pathway, which plays a role in the formation and growth of numerous cancers. Tarceva is designed to inhibit the tyrosine kinase activity of the HER1 signaling pathway inside the cell.

Development Status In the first quarter of 2009, OSI Pharmaceuticals in conjunction with Genentech, submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for first-line maintenance therapy for advanced non-small cell lung cancer. This submission has a Prescription Drug User Fee Act (PDUFA) date of on or about January 18, 2010.

Tarceva is being evaluated in Phase III clinical trials for adjuvant non-small cell lung cancer, first-line metastastic EGFR mutant-positive non-small cell lung cancer, and in combination with Avastin for first-line metastatic, non-small cell lung cancer. Clinical trials are also ongoing to planned evaluating Tarceva in combination with investigational targeted agents, such as MetMAb, PI3 Kinase Inhibitor (GDC-0941), and pertuzumab.

Tarceva is being developed in collaboration with OSI Pharmaceuticals, Inc.

Approved Uses

• In November 2004, the FDA approved Tarceva monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Results from two multicenter, placebo-controlled, randomized Phase III trials conducted in first-line patients with locally advanced or metastatic NSCLC showed no clinical benefit with the concurrent administration of Tarceva with platinum-based chemotherapy, and its use is not recommended in that setting.
• In November 2005, the FDA approved Tarceva in combination with gemcitabine chemotherapy for the first-line treatment of patients with locally advanced, inoperable or metastatic pancreatic cancer.

Important Safety Information There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events including deaths in patients taking Tarceva. Serious side effects (including deaths) in patients taking Tarceva include liver and/or kidney problems; gastrointestinal (GI) perforations (the development of a hole in the stomach, small intestine, or large intestine); and severe blistering skin reactions including cases similar to Stevens-Johnson syndrome. Patients taking Tarceva plus gemcitabine were more likely to experience bleeding and clotting problems such as heart attack or stroke. Eye irritation and damage to the cornea have been reported in patients taking Tarceva. Women should avoid becoming pregnant and avoid breastfeeding while taking Tarceva. Patients should call their doctor right away if they have these signs or symptoms: new or worsening skin rash; serious or ongoing diarrhea, nausea, loss of appetite, vomiting, or stomach pain; new or worsening shortness of breath or cough; fever; eye irritation. Rash and diarrhea were the most common side effects associated with Tarceva in the non-small cell lung cancer clinical study. Fatigue, rash, nausea, loss of appetite, and diarrhea were the most common side effects associated with Tarceva plus gemcitabine therapy in the pancreatic cancer clinical study.

For Tarceva full prescribing information, including additional important safety information, please visit http://www.tarceva.com or call 1-877-TARCEVA.

Additional Information on Clinical Trials For inquiries about our clinical trials, please submit a request through our information request form or call (888) 662-6728.

National Institutes of Health Website: www.clinicaltrials.gov

August 2009