Frequently Asked Questions

• Have there been any head-to-head comparisons between Tarceva and chemotherapy in advanced non-small cell lung cancer (NSCLC)?
• In which types of patients with advanced NSCLC is Tarceva use appropriate?
• What are the indications for Tarceva?
• What is the rationale for maintenance therapy?
• What types of patients are appropriate for maintenance therapy?
• Are there any potential drug interactions with Tarceva?
• Does smoking affect the bioavailability of Tarceva?
• Are there insurance information resources available for Tarceva?
• How do I manage rash?
• How do I manage diarrhea?
• What if the dose of Tarceva needs to be discontinued, reduced, or interrupted?
• What are the serious adverse reactions observed with Tarceva in the treatment of advanced NSCLC?
• What are the most common adverse reactions with Tarceva in NSCLC?
• What is the Important Safety Information for Tarceva I should know?
• What is the recommended dosing for Tarceva?

Q: Have there been any head-to-head comparisons between Tarceva and chemotherapy in advanced non-small cell lung cancer (NSCLC)?

A: The EURTAC trial evaluated the efficacy and safety of Tarceva monotherapy 150 mg in patients who had metastatic NSCLC with EGFR mutations (exon 19 deletions or exon 21 [L858R] substitution mutations).¹

• Back to top

Q: In which types of patients with advanced NSCLC is Tarceva use appropriate?

A: As first-line therapy for metastatic NSCLC¹:

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.

As maintenence therapy in locally advanced or metastatic NSCLC¹:

Tarceva monotherapy is indicated for the maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.

• Tarceva is the only FDA-approved oral option for NSCLC maintenance therapy in advanced NSCLC.¹

As therapy for relapsed or refractory locally advanced or metastatic NSCLC:

Tarceva monotherapy is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.

• Tarceva is the only oral therapy that is FDA approved for the treatment of relapsed or refractory advanced NSCLC in a broad patient population.¹

Limitations of use¹:

• 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.

• Back to top

Q: What are the indications for Tarceva?

A: 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 non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
• The treatment of patients with locally advanced or metastatic non-small cell lung cancer 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.

• Back to top

Q: What is the rationale for maintenance therapy?

A: Tarceva maintenance therapy in stage IIIB/IV NSCLC ensures that patients receive immediate active therapy after first-line treatment, which has been proven to prolong overall survival.^1,2

• In several trials studying different maintenance regimens, 31% of patients given a treatment holiday did not receive any further active therapy.^3-5
  • Rapid progression, declining performance status, and increased symptom burden may render patients unsuitable to receive further treatment.^4,6
• Immediate maintenance therapy with Tarceva enables more patients to receive active therapy after first-line treatment.^2,5
• As maintenance therapy, Tarceva offers:
  • An oral formulation that provides an alternative to intravenous infusions.¹
  • A proven survival benefit (HR=0.81; 95% CI=0.70-0.95; P=0.0088; median: 12.0 months with Tarceva vs 11.0 months with placebo).¹

• Back to top

Q: What types of patients are appropriate for maintenance therapy?

A: Maintenance therapy is treatment with a different agent that begins immediately after first-line chemotherapy in patients without disease progression.

Tarceva is indicated for the maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.

Limitations of use¹:

• 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.

• Back to top

Q: Are there any potential drug interactions with Tarceva?

A: Erlotinib is metabolized predominantly by CYP3A4, and inhibitors of CYP3A4 would be expected to increase exposure. Caution should be used during co-treatment with Tarceva and ketoconazole or other strong CYP3A4 inhibitors such as, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, and grapefruit or grapefruit juice.¹

The CYP3A4 inducer rifampicin has been shown to decrease erlotinib AUC; thus, alternate treatments lacking CYP3A4-inducing activity are strongly recommended. In the absence of an alternative treatment, Tarceva dose modification should be considered. If the Tarceva dose is adjusted upward, the dose will need to be reduced immediately to the indicated starting dose upon discontinuation of rifampicin or other CYP3A4 inducers such as, but not limited to, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John's wort.¹

Drugs that alter the pH of the upper GI tract may alter the solubility of erlotinib and reduce its bioavailability. The concomitant use of proton pump inhibitors such as omeprazole with Tarceva should be avoided if possible. If patients need to be treated with an H₂-receptor antagonist such as ranitidine, it should be used in a staggered manner. Tarceva must be taken once a day, 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.¹

The combination of Tarceva and a statin may increase the potential for statin-induced myopathy, including rhabdomyolysis, which was observed rarely. The mechanism of this interaction is not clear.

Please see additional Important Safety Information.

• Back to top

Q: Does smoking affect the bioavailability of Tarceva?

A: Cigarette smoking has been shown to reduce erlotinib exposure. Patients should be advised to stop smoking. If a patient continues to smoke, a cautious increase in the dose of Tarceva not exceeding 300 mg may be considered, while monitoring the patient's safety. However, efficacy and long-term safety (>14 days) of a dose higher than the recommended starting doses have not been established in patients who continue to smoke cigarettes. If the Tarceva dose is adjusted upward, the dose should be reduced immediately to the indicated starting dose upon cessation of smoking.

• Back to top

Q: Are there insurance information resources available for Tarceva?

A: Tarceva Access Solutions^® helps resolve access and reimbursement issues for individual patients every day. Our dedicated in-house Specialists help bring patient treatment and practice solutions together. Specialists can also provide information regarding the following programs:

• Genentech BioOncology Co-pay Card Program*
  • Tarceva Access Solutions is committed to helping patients access the medicine they need with the Genentech BioOncology Co-pay Card. For eligible patients, the card covers 80% of the out-of-pocket cost^† for patients' Genentech cancer treatment; patients are responsible for the remaining 20% of the out-of-pocket cost.
• Tarceva Dose Modification Exchange Program
  • For patients who have had their dose of Tarceva reduced, the Dose Modification Exchange Program can replace the tablets they have left at no additional cost.
• Genentech^® Access to Care Foundation (GATCF)
  • The Genentech^® Access to Care Foundation was established to help patients with unmet medical needs who are uninsured or rendered uninsured by payer denial and who meet specific financial and medical criteria to receive proper medical treatment.
  • The patient must meet certain eligibility criteria, including income restrictions, to be eligible for resources from the GATCF.
• GATCF Extension for Medicare Part D Patients
  • Patients in Medicare Part D used to face very large co-pays for Tarceva because of a gap in coverage. But now, help from the GATCF has been extended to patients in Medicare Part D.
  • Under this expansion, eligible patients can receive Tarceva from the GATCF at no cost. Genentech has worked with Medicare to make this happen.

For more information on these programs, please call 1 (888) 249-4918 or visit
www.Genentech-Access.com/Tarceva.

*Certain restrictions apply.
^†Out-of-pocket costs are defined as co-pay, co-insurance, or deductible.

• Back to top

Q: How do I manage rash?

A: Tarceva should be withheld in cases of severe rash that is not responsive to medical treatment.¹

For more information about rash assessment and management, click here.

• Back to top

Q: How do I manage diarrhea?

A: Diarrhea can usually be managed with loperamide. Tarceva should be withheld in cases of persistent severe diarrhea not responsive to medical management.

For more information about diarrhea assessment and management, click here.

• Back to top

Q: What if the dose of Tarceva needs to be discontinued, reduced, or interrupted?

A: Discontinue Tarceva for:

• Interstitial Lung Disease (ILD).
• Severe hepatic toxicity that does not improve significantly or resolve within three weeks.
• Gastrointestinal perforation.
• Severe bullous, blistering or exfoliating skin conditions.
• Corneal perforation or severe ulceration.

Withhold Tarceva:

• During diagnostic evaluation for possible ILD.
• For severe (CTCAE grade 3/4) renal toxicity, and consider discontinuation of Tarceva.
• In patients without pre-existing hepatic impairment for total bilirubin levels greater than 3 times the upper limit of normal or transaminases greater than 5 times the upper limit of normal, and consider discontinuation of Tarceva.
• In patients with pre-existing hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases values over baseline and consider discontinuation of Tarceva.
• For persistent severe diarrhea not responsive to medical management (e.g., loperamide).
• For severe rash not responsive to medical management.
• For keratitis of (NCI-CTC version 4.0) grade 3/4 or for grade 2 lasting more than 2 weeks.
• For acute/worsening ocular disorders such as eye pain, and consider discontinuation of Tarceva.

Reduce Tarceva 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 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.

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 such as ranitidine 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.

• Back to top

Q: What are the serious adverse reactions observed with Tarceva in the treatment of advanced NSCLC?

A: Adverse reactions, including fatalities, associated with Tarceva in advanced NSCLC include¹:

• Interstitial lung disease (ILD)
• Renal failure
• Hepatotoxicity with or without hepatic impairment
• Gastrointestinal perforation
• Bullous and exfoliative skin disorders
• Myocardial infarction/ischemia
• Cerebrovascular accident
• Microangiopathic hemolytic anemia with thrombocytopenia
• Ocular disorders
• Hemorrhage in patients taking warfarin
• Embryo-fetal toxicity

• Back to top

Q: What are the most common adverse reactions with Tarceva in NSCLC?

A: Serious adverse reactions have occurred with Tarceva; the most common adverse reactions associated with Tarceva are generally manageable.¹

• The most common adverse reactions for Tarceva in the first-line treatment of patients with metastatic NSCLC who have EGFR mutations were diarrhea, asthenia, rash,* cough, dyspnea, and decreased appetite.¹
• The most common adverse reactions in patients with advanced NSCLC receiving Tarceva monotherapy 150 mg as maintenance therapy were rash* and diarrhea.¹
• The most common adverse reactions in patients receiving Tarceva monotherapy 150 mg for relapsed or refractory advanced NSCLC were rash* and diarrhea.¹

*

Rash is a composite term; see Rash characteristics for more information.

Please see adverse reactions section or the full Prescribing Information.

• Back to top

Q: What is the Important Safety Information for Tarceva I should know?

A: 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.

• Back to top

Q: What is the recommended dosing for Tarceva?

A: The recommended once-daily dose of Tarceva for the treatment of advanced NSCLC is 150 mg taken orally on an empty stomach. Treatment should continue until disease progression or unacceptable toxicity occur.¹

Erlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%. Patients should be instructed to take Tarceva on an empty stomach at least one hour before or two hours after the ingestion of food.¹

An unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation, may occur above the recommended dose.¹

• Back to top