Full Prescribing Information
Dear Healthcare Provider Letter (219K/PDF)

Tarceva® (erlotinib) is a small molecule human epidermal growth factor type 1/epidermal growth factor receptor (HER1/EGFR) inhibitor which demonstrated, in a Phase III clinical trial, an increased survival in advanced non-small cell lung cancer (NSCLC) patients. In a Phase III trial, Tarceva has also shown an improvement in overall survival when added to gemcitabine chemotherapy as initial treatment for advanced pancreatic cancer.

Status In November 2004, the U.S. Food and Drug Administration (FDA) approved Tarceva (150 mg) 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.

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.

Tarceva was approved under the FDA's Pilot Program for Continuous Marketing Applications, a new program designed for investigational products, such as Tarceva, that have been given Fast Track status and that have demonstrated significant promise in clinical trials as a therapeutic advance over available therapy for a disease or condition. Tarceva is approved across the European Union and in Canada.

The FDA based its approval for Tarceva in NSCLC on results from a randomized double-blind, placebo-controlled pivotal Phase III trial of patients with second- and third-line advanced NSCLC. The trial included 731 patients with advanced NSCLC for whom one or more chemotherapy regimens had failed. Tarceva met its primary endpoint of improving overall survival (hazard ratio = 0.73). In addition to demonstrating a 42 percent improvement in median survival (6.7 versus 4.7 months), 31.2 percent of patients receiving Tarceva in the study were alive after one year versus 21.5 percent in the placebo arm. Tarceva also met all secondary endpoints of the trial, including delaying time to symptom deterioration, improving progression-free survival, and increasing tumor response rate.

In November 2005, the FDA approved Tarceva (100 mg) in combination with gemcitabine chemotherapy for the treatment of locally advanced, inoperable or metastatic pancreatic cancer in patients who have not received previous chemotherapy.

The FDA based its approval decision for Tarceva on results from a randomized double-blind, placebo-controlled Phase III clinical study of Tarceva, in combination with gemcitabine chemotherapy in 569 patients with unresectable locally advanced or metastatic pancreatic cancer. The study met its primary endpoint of improving overall survival by 23 percent (hazard ratio = 0.81). After one year, 24 percent of patients receiving Tarceva plus gemcitabine were alive compared to 19 percent of patients receiving gemcitabine plus placebo. A statistically significant improvement in progression-free survival (hazard ratio = 0.76) also was demonstrated.

Safety

• There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events, including fatalities, in patients receiving Tarceva for treatment of NSCLC, pancreatic cancer or other advanced solid tumors.
• Cases of hepatic failure, hepatorenal syndrome, acute renal failure (all including fatalities), and renal insufficiency have been reported during use of TARCEVA.
• In the pancreatic cancer trial, other serious adverse reactions associated with Tarceva plus gemcitabine and which may have included fatalities, were myocardial infarction/ischemia, cerebrovascular accident and microangiopathic hemolytic anemia with thrombocytopenia.
• When receiving Tarceva therapy, women should be advised against becoming pregnant or breastfeeding. Tarceva is pregnancy category D.
• The most common adverse reactions in patients with NSCLC receiving Tarceva monotherapy 150 mg were rash and diarrhea.
• The most common adverse reactions in patients with pancreatic cancer receiving Tarceva 100 mg plus gemcitabine were fatigue, rash, nausea, anorexia and diarrhea.

View full prescribing information for additional safety information.

Proposed Mechanism of Action Tarceva is a small molecule designed to target the human epidermal growth factor receptor (HER1) pathway, which is one of the factors critical to cell growth in non-small cell lung and pancreatic cancers. HER1, also known as EGFR, is a component of the HER signaling pathway, which plays a role in the formation and growth of non-small cell lung and pancreatic cancers. Tarceva is designed to inhibit the tyrosine kinase activity of the HER1 signaling pathway inside the cell.

The clinical anti-tumor action of erlotinib is not fully characterized.

Non-Small Cell Lung Cancer According to the American Cancer Society, lung cancer is one of the most common cancers, with newly diagnosed cases expected to exceed 215,000 in the United States this year. Lung cancer is the leading cause of cancer deaths, accounting for approximately 30 percent of all cancer deaths (more than breast, colon, and liver cancers combined) expected to occur in the U.S in 2008. In 2005, lung cancer killed an estimated 1.3 million people worldwide.

Pancreatic Cancer Although pancreatic cancer accounts for just two percent of new cancer cases in the United States, it is the fourth leading cause of all cancer deaths. The American Cancer Society predicts that in 2008 almost 38,000 people in the United States will be diagnosed with pancreatic cancer, and about 34,000 will die of the disease. The most prevalent pancreatic cancer type is exocrine cancer. Most pancreatic tumors originate in the exocrine duct cells or in the cells that produce digestive enzymes (acinar cells). Called adenocarcinomas, these tumors account for nearly 95 percent of pancreatic cancers.