Advanced Non-Small Cell Lung Cancer (NSCLC) Indications

Tarceva is indicated for:

• The first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.
• The maintenance treatment of patients with locally advanced or metastatic NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
• The treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.

Limitations of use:

• Tarceva is not recommended for use in combination with platinum-based chemotherapy.
• Safety and efficacy of Tarceva have not been evaluated as first-line treatment in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution.

Important Safety Information

DOSE MODIFICATIONS

• Reduce Tarceva dose by 50 mg decrements:
  • If severe reactions occur with concomitant use of strong CYP3A4 inhibitors [such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, or grapefruit or grapefruit juice] or when using concomitantly with an inhibitor of both CYP3A4 and CYP1A2 (e.g., ciprofloxacin). Avoid concomitant use if possible.
  • When restarting therapy following withholding treatment for a dose-limiting toxicity that has resolved to baseline or grade ≤1.
• Increase Tarceva dosage by 50 mg increments as tolerated for:
  • Concomitant use with CYP3A4 inducers such as rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John's wort. Increase doses by 50 mg increments at 2 week intervals to a maximum of 450 mg. Avoid concomitant use if possible.
  • Concurrent cigarette smoking. Increase by 50 mg increments at 2 week intervals to a maximum of 300 mg. Immediately reduce the dose of Tarceva to the recommended dose (150 mg or 100 mg daily) upon cessation of smoking.
• For drugs affecting gastric pH:
  • Avoid concomitant use of Tarceva with proton pump inhibitors if possible. Separation of doses may not eliminate the interaction since proton pump inhibitors affect the pH of the upper GI tract for an extended period.
  • If treatment with an H₂-receptor antagonist is required, Tarceva must be taken 10 hours after the H₂-receptor antagonist dosing and at least 2 hours before the next dose of the H₂-receptor antagonist.
  • Although the effect of antacids on erlotinib pharmacokinetics has not been evaluated, the antacid dose and the Tarceva dose should be separated by several hours, if an antacid is necessary.

CONTRAINDICATIONS

None

WARNINGS AND PRECAUTIONS

• Interstitial Lung Disease (ILD):
  • Cases of serious ILD, including fatal cases, can occur with Tarceva treatment.
  • Withhold Tarceva for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, permanently discontinue Tarceva.
• Renal Failure:
  • Hepatorenal syndrome, severe acute renal failure including fatal cases, and renal insufficiency can occur with Tarceva treatment. Renal failure may arise from exacerbation of underlying baseline hepatic impairment or severe dehydration.
  • Withhold Tarceva in patients developing severe renal impairment until renal toxicity is resolved. Perform periodic monitoring of renal function and serum electrolytes during Tarceva treatment.
• Hepatotoxicity with or without Hepatic Impairment:
  • Hepatic failure and hepatorenal syndrome, including fatal cases, can occur with Tarceva treatment in patients with normal hepatic function; the risk of hepatic toxicity is increased in patients with baseline hepatic impairment.
  • Perform periodic liver testing (transaminases, bilirubin, and alkaline phosphatase) during treatment with Tarceva. Increased frequency of monitoring of liver function is required for patients with pre-existing hepatic impairment or biliary obstruction.
  • Withhold Tarceva in patients without pre-existing hepatic impairment for total bilirubin >3 x ULN and/or transaminases >5 x ULN. Withhold Tarceva in patients with pre-existing hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases value over baseline.
  • Discontinue Tarceva in patients whose abnormal liver tests meeting the above criteria do not improve significantly or resolve within 3 weeks.
• Gastrointestinal Perforation:
  • Gastrointestinal perforation, including fatal cases, can occur with Tarceva treatment. Patients receiving concomitant anti-angiogenic agents, corticosteroids, NSAIDs, or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease may be at increased risk of perforation.
  • Permanently discontinue Tarceva in patients who develop gastrointestinal perforation.
• Bullous and Exfoliative Skin Disorders:
  • Bullous, blistering and exfoliative skin conditions, including cases suggestive of Stevens-Johnson syndrome/toxic epidermal necrolysis, which in some cases were fatal, can occur with Tarceva treatment.
  • Discontinue Tarceva treatment if the patient develops severe bullous, blistering or exfoliating conditions.
• Myocardial Infarction (MI)/Ischemia:
  • In the pancreatic carcinoma trial, MI/ischemia was reported in patients, including fatal cases of MI. In the pooled incidence in the 3 monotherapy lung studies cases of MI/ischemia were reported.
• Cerebrovascular Accident:
  • In the pancreatic carcinoma trial, cerebrovascular accident was reported in patients, including a fatal case. In the pooled incidence in the 3 monotherapy lung studies cases of cerebrovascular accident were reported.
• Microangiopathic Hemolytic Anemia with Thrombocytopenia:
  • In the pooled incidence of 3 monotherapy lung cancer studies and the pancreatic carcinoma trial, cases of microangiopathic hemolytic anemia with thrombocytopenia were reported.
• Ocular Disorders:
  • Corneal perforation or ulceration can occur with Tarceva treatment, including abnormal eyelash growth, keratoconjunctivitis sicca or keratitis.
  • Interrupt or discontinue Tarceva therapy if patients present with acute/worsening ocular disorders such as eye pain.
• Hemorrhage in patients taking Warfarin:
  • Severe and fatal hemorrhage associated with International Normalized Ratio (INR) elevations can occur when Tarceva and warfarin are administered concurrently.
  • Regularly monitor prothrombin time and INR during Tarceva treatment in patients taking warfarin or other coumarin-derivative anticoagulants.
• Embryo-Fetal Toxicity:
  • Tarceva is category D. Based on its mechanism of action, Tarceva can cause fetal harm when administered to a pregnant woman. If Tarceva is used during pregnancy, or if the patient becomes pregnant while taking Tarceva, the patient should be apprised of the potential hazard to a fetus.
  • Advise females of reproductive potential to use highly effective contraception during therapy and for at least 2 weeks after the last dose of Tarceva. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking Tarceva.

MOST COMMON ADVERSE REACTIONS

• NSCLC — First-Line With EGFR Mutations:
  • Diarrhea, asthenia, rash, cough, dyspnea, and decreased appetite.
  • Grade 3/4 (NCI-CTC Version 3.0) adverse reactions were rash (14%) and diarrhea (5%). In Tarceva-treated patients, the most frequently reported adverse reactions leading to dose modification were rash (13%), diarrhea (10%), and asthenia (3.6%).
• NSCLC — Maintenance:
  • Rash and diarrhea.
  • Grade 3/4 (NCI-CTC Version 3.0) adverse reactions were rash (9%) and diarrhea (2%). Rash and diarrhea resulted in dose reductions or interruption (5% and 3%, respectively) and discontinuation (1% and 0.5%, respectively) of Tarceva-treated patients.
• NSCLC — Second/Third-Line:
  • Rash and diarrhea.
  • Grade 3/4 (NCI-CTC Version 2.0) adverse reactions were rash (9%) and diarrhea (6%). Rash and diarrhea each resulted in dose reductions (6% and 1%, respectively) and discontinuation in 1% of Tarceva-treated patients.
• Pancreatic Cancer — Tarceva With Gemcitabine:
  • Fatigue, rash, nausea, anorexia, and diarrhea.
  • Grade 3/4 (NCI-CTC version 2.0) adverse reactions were rash (5%) and diarrhea (5%). Rash and diarrhea each resulted in dose reductions in 2% of patients and discontinuation in up to 1% of patients receiving Tarceva plus gemcitabine.

You may report side effects to the FDA at 1 (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1 (888) 835-2555.

• For additional Important Safety Information, please see the Tarceva full Prescribing Information.