Full Prescribing Information

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.

• In clinical studies, there were infrequent reports of lung injuries similar to Interstitial Lung Disease (ILD)-like events in patients taking Tarceva for the treatment of non-small cell lung cancer (NSCLC) or other advanced solid tumors. Reports of these ILD-like lung injuries have been serious and have included deaths in some patients.
• Liver and/or kidney problems (including deaths) have been reported in some patients taking Tarceva.
• Holes that formed in the stomach, small intestine, or large bowel (including deaths) have been reported in patients taking Tarceva.
• Severe blistering skin reactions including cases similar to Stevens-Johnson syndrome (including deaths) have been reported in patients taking Tarceva.

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.

• Eye irritation and damage to the cornea have been reported in patients taking Tarceva. Patients should tell their doctor about eye problems, including eye pain that gets worse.
• Difficulty with blood clotting, and bleeding events, including gastrointestinal and non-gastrointestinal bleeding, have been reported in clinical studies.
• Tarceva may cause harm to an unborn baby or may cause possible risk of pregnancy loss. Women should avoid becoming pregnant and avoid breastfeeding while taking Tarceva.

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. Fatigue, rash, nausea, loss of appetite, and diarrhea were the most common side effects associated with Tarceva plus gemcitabine therapy in a large clinical study.

Patients taking Tarceva plus gemcitabine were more likely to experience bleeding and clotting problems such as heart attack or stroke.

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.

In April 2010, Tarceva was approved by the FDA for patients with advanced-stage non-small cell lung cancer (NSCLC) whose cancer has not spread or grown after initial treatment with certain types of chemotherapy. Tarceva is not meant to be used at the same time as certain types of chemotherapy for NSCLC.

Safety

• In clinical studies, there were infrequent reports of lung injuries similar to Interstitial Lung Disease (ILD)-like events in patients taking Tarceva for the treatment of non-small cell lung cancer (NSCLC) or other advanced solid tumors. Reports of these ILD-like lung injuries have been serious and have included deaths in some patients.
• Liver and/or kidney problems (including deaths) have been reported in some patients taking Tarceva.
• Holes that formed in the stomach, small intestine, or large bowel (including deaths) have been reported in patients taking Tarceva.
• Severe blistering skin reactions including cases similar to Stevens-Johnson syndrome (including deaths) have been reported in patients taking Tarceva.
• 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. Patients should tell their doctor about eye problems, including eye pain that gets worse.
• Difficulty with blood clotting, and bleeding events, including gastrointestinal and non-gastrointestinal bleeding, have been reported in clinical studies.
• Tarceva may cause harm to an unborn baby or may cause possible risk of pregnancy loss. 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.
• Patients who smoke should stop smoking while taking Tarceva, as it may affect how well Tarceva works for them. If patients continue to smoke they should speak to their doctor before taking Tarceva.
• Patients should let their doctor know if they are taking other prescription or over-the-counter drugs or herbal supplements before they start taking Tarceva, and should not start taking any new drugs or herbal supplements before talking to their doctor. Patients should not eat grapefruit or drink grapefruit juice while taking Tarceva. Tarceva may also affect other medications patients are taking.
• Rash and diarrhea were the most common side effects associated with Tarceva in the NSCLC clinical study. Patients may also have other changes in their skin.
• 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.

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.