Frequently Asked Questions
- Have there been any head-to-head comparisons between Tarceva and chemotherapy in NSCLC?
- In which types of NSCLC patients is Tarceva use appropriate?
- What are Tarceva's indications?
- What is maintenance therapy?
- What types of patients are appropriate for maintenance therapy?
- Are there any potential drug interactions with Tarceva?
- Are there insurance information resources available for Tarceva?
- How do I manage rash?
- How do I manage diarrhea?
- What if my patient needs a dose reduction?
- What are the most common adverse reactions with Tarceva?
- 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 NSCLC?
A: There have been no head-to-head studies comparing Tarceva and chemotherapy.
In the SATURN trial for NSCLC maintenance therapy, Tarceva monotherapy 150 mg was compared with placebo in stage IIIB/IV NSCLC patients. In the BR.21 trial for relapsed or refractory NSCLC, Tarceva monotherapy 150 mg was compared with placebo in stage IIIB/IV NSCLC patients.
Q: In which types of NSCLC patients is Tarceva use appropriate?
A:
As maintenance therapy in advanced NSCLC
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.
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 [carboplatin and paclitaxel or gemcitabine and cisplatin] and its use is not recommended in that setting.
The results from the Tarceva maintenance NSCLC pivotal trial (SATURN; N=889) showed an improvement in survival among an unselected population.
In the pivotal clinical trial for maintenance treatment of NSCLC, there was a significant survival benefit for a large, unselected group of patients receiving Tarceva monotherapy. Tarceva significantly improved overall survival by 23% vs placebo in these pretreated NSCLC patients (HR=0.81; 95% CI=0.70-0.95; P=0.0088).
As therapy for relapsed or refractory 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.
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 [carboplatin and paclitaxel or gemcitabine and cisplatin] and its use is not recommended in that setting.
The results from the Tarceva relapsed/refractory NSCLC pivotal trial (BR.21; N=731) showed an improvement in survival among an unselected population.
In the pivotal clinical trial for treatment of relapsed or refractory NSCLC, there was a significant survival benefit for a large, unselected group of patients receiving Tarceva monotherapy. Tarceva significantly improved overall survival by 37% vs placebo in these pretreated NSCLC patients (HR=0.73; 95% CI=0.61-0.86; P<0.001; median: 6.7 months with Tarceva vs 4.7 months with placebo).
To learn more about Tarceva safety information, please see Tarceva important safety information and the FAQs about Tarceva common and serious adverse reactions included in this section.
Q: What are Tarceva’s indications?
A:
Non-small cell lung cancer (NSCLC) indications
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.
- 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 [carboplatin and paclitaxel or gemcitabine and cisplatin] and its use is not recommended in that setting.
Pancreatic cancer indication
Tarceva in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
Q: What is maintenance therapy?
A: Maintenance therapy may allow more patients to receive additional lines of therapy and may prolong their survival. Many patients do not receive second-line treatment. Rapid progression, declining performance status, and increased symptom burden may render patients unsuitable to receive further treatment. Only approximately 50% of patients in recent clinical trials received second-line treatment, in part due to complications associated with disease progression. Maintenance treatment may help increase post–first-line treatment rates. Two pivotal phase III maintenance studies have demonstrated a survival improvement.
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 monotherapy 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.
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 [carboplatin and paclitaxel or gemcitabine and cisplatin] and its use is not recommended in that setting.
Q: Are there any potential drug interactions with Tarceva?
A: The potent CYP3A4 inhibitor ketoconazole has been shown to increase erlotinib AUC; thus, caution should be used during co-treatment with Tarceva and ketoconazole or other CYP3A4 inhibitors such as, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, and grapefruit and grapefruit juice. When Tarceva was co-administered with ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the erlotinib AUC increased by 39%.
The CYP3A4 inducer rifampicin has been shown to decrease erlotinib AUC; thus, alternate treatments lacking CYP3A4-inducing activity should be considered. In the absence of an alternative, Tarceva dose modification should be considered during co-treatment with rifampicin and other CYP3A4 inducers such as, but not limited to, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John’s Wort.
Drugs that alter the pH of the upper GI tract may alter the solubility of erlotinib and reduce its bioavailability. Increasing the dose of Tarceva when co-administered with such agents is not likely to compensate for the loss of exposure. Co-administration of Tarceva with omeprazole, a proton pump inhibitor, decreased the erlotinib AUC by 46%. Since proton pump inhibitors affect pH of the upper GI tract for an extended period, separation of doses may not eliminate the interaction. The concomitant use of proton pump inhibitors with Tarceva should be avoided if possible. Co-administration of Tarceva with 300 mg ranitidine, an H2-receptor antagonist, decreased erlotinib AUC by 33%. When Tarceva was administered with ranitidine 150 mg twice daily (at least 10 hours after the previous ranitidine evening dose and 2 hours before the ranitidine morning dose), the erlotinib AUC decreased by 15%. 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.
Q: Are there insurance information resources available for Tarceva?
A: Tarceva Access Solutions provides coverage and reimbursement support, patient assistance, and informational resources for both healthcare providers and their patients.
If uninsured or financially challenged patients need help covering the cost of Tarceva, the experts at Tarceva Access Solutions can help them with this issue. An Access Solutions specialist can also provide information regarding the following programs:
- Tarceva Co-Pay Card Program
- Genentech® Access to Care Foundation (GATCF)
- GATCF Extension for Medicare Part D Patients
- Tarceva Dose Modification Program
Tarceva Access Solutions helps to resolve specific access and reimbursement issues for individual patients every day. Our dedicated Specialists help bring patient treatment and practice solutions together. To speak live with one of our Specialists, call (888) 249-4918 from 6 AM to 5 PM PT Monday to Friday or visit TarcevaAccessSolutions.com.
A: In the pivotal clinical trial for maintenance treatment of NSCLC, grades 3/4 rash occurred in 6.0% of Tarceva-treated patients. 5.1% of patients needed dose reduction or interruption of therapy, and 1.2% of patients discontinued treatment due to rash.
In the pivotal clinical trial for treatment of relapsed/refractory NSCLC, grades 3/4 rash occurred in 9% of Tarceva-treated patients. Six percent of patients needed dose reduction, and 1% of patients discontinued treatment due to rash.
For patients with intolerable rash, the PI recommends that you reduce the dose in 50-mg decrements. Tarceva is available in three tablet strengths: 150 mg, 100 mg, and 25 mg.
Clinical trial protocol for rash management included minocycline, topical tetracycline or clindamycin, topical silver sulfadiazine, diphenhydramine, and oral prednisone. The efficacy of these agents was not assessed in the analysis of the BR.21 trial.
A: In the SATURN clinical trial evaluating Tarceva as maintenance therapy for NSCLC, grades 3/4 diarrhea occurred in 1.8% of patients. 2.8% of patients needed dose reduction or interruption of therapy, and 0.5% of patients discontinued treatment due to diarrhea.
In the BR.21 clinical trial evaluating Tarceva for treatment of relapsed/refractory NSCLC, grades 3/4 diarrhea occurred in 6% of patients. One percent of patients needed dose reduction, and 1% of patients discontinued treatment due to diarrhea.
Diarrhea can usually be managed with loperamide. Patients with severe diarrhea who are unresponsive to loperamide or who become dehydrated may require dose reduction or temporary interruption of therapy. For patients with severe diarrhea who become dehydrated, consider treatment with oral rehydration therapy.
When dose reduction is necessary, the Tarceva dose should be reduced in 50-mg decrements.
Q: What if my patient needs a dose reduction?
A: In the pivotal SATURN trial evaluating Tarceva as maintenance therapy for NSCLC, the most common adverse reactions in patients receiving single-agent Tarceva 150 mg were rash and diarrhea. Grades 3 and 4 rash and diarrhea occurred in 6.0% and 1.8% of Tarceva-treated patients, respectively. Dose reduction or interruption of therapy for rash and diarrhea occurred in 5.1% and 2.8% of patients, respectively.
In the pivotal BR.21 trial evaluating Tarceva for treatment of relapsed/refractory NSCLC, 81% of patients tolerated the 150-mg dose. Dose reductions were allowed in the single-agent phase III trial and happened in 19% of patients. Six percent and 1% of patients needed dose reduction for rash and diarrhea, respectively.
If patients experience intolerable adverse reactions, such as intolerable skin reactions, intolerable diarrhea that is unresponsive to loperamide or that causes dehydration, or severe liver function test abnormalities, consider dose reduction or interruption of Tarceva.
Tarceva is also available in 100-mg and 25-mg dosage strengths to allow for dose reduction when appropriate.
When dose reduction is necessary, the Tarceva dose should be reduced by 50-mg decrements.
Patients with moderate/tolerable (grade 2) or severe/intolerable (grade ≥3) reactions may be appropriate for treatment with medically managed supportive care.
Patients with grade ≥3 reactions or those who cannot be managed medically may require dose reduction or temporary interruption of therapy.
The pivotal phase III protocol specified the following dose-modification guidelines for grade ≥3 rash or diarrhea that could not be medically managed:
- Hold the dose until symptom severity is grade ≤1
- Reduce the dose by a 50-mg decrement
When dose reduction was necessary, the dose could not be re-escalated for the remainder of the study.
In Tarceva-treated patients, treatment discontinuation may be required for the following adverse reactions:
- Interstitial Lung Disease (ILD) (appropriate treatment should be instituted as necessary)
- Hepatic failure or gastrointestinal perforation
- Severe bullous, blistering, or exfoliative skin conditions
- Acute/worsening ocular disorders
In Tarceva-treated patients, dose reduction and/or interruption may be required for the following adverse reactions:
- Acute onset of new or progressive pulmonary symptoms, such as dyspnea, cough, or fever (pending diagnostic evaluation)
- Dehydration in patients at risk for renal failure
- Severe bullous, blistering, or exfoliative skin conditions
- Acute/worsening ocular disorders
- Severe diarrhea in patients who are unresponsive to loperamide or who become dehydrated
- Severe skin reactions
Q: What are the most common adverse reactions with Tarceva?
A: In the single-agent phase III SATURN trial evaluating Tarceva as maintenance therapy for NSCLC, the most common adverse reactions, rash and diarrhea, were generally mild to moderate. Rash and diarrhea resulted in treatment discontinuation in 1.2% and 0.5% of Tarceva-treated patients, respectively.
| Tarceva 150 mg n=433 |
Placebo n=445 |
|||||
| NCI-CTC Grade | Any grade | Grade 3 | Grade 4 | Any grade | Grade 3 | Grade 4 |
| MedDRA preferred term | % | % | % | % | % | % |
| Rash | 49.2 | 6.0 | 0 | 5.8 | 0 | 0 |
| Diarrhea | 20.3 | 1.8 | 0 | 4.5 | 0 | 0 |
| Anorexia | 9.2 | <1 | 0 | 4.9 | <1 | 0 |
| Fatigue | 9.0 | 1.8 | 0 | 5.8 | 1.1 | 0 |
| Pruritus | 7.4 | <1 | 0 | 2.7 | 0 | 0 |
| Acne | 6.2 | <1 | 0 | 0 | 0 | 0 |
| Dermatitis Acneiform | 4.6 | <1 | 0 | 1.1 | 0 | 0 |
| Dry skin | 4.4 | 0 | 0 | <1 | 0 | 0 |
| Weight Decreased | 3.9 | <1 | 0 | <1 | 0 | 0 |
| Paronychia | 3.9 | <1 | 0 | 0 | 0 | 0 |
In the pivotal BR.21 trial evaluating Tarceva for treatment of relapsed/refractory NSCLC, the most common adverse reactions, rash and diarrhea, were generally mild to moderate. Each resulted in treatment discontinuation in 1% of Tarceva-treated patients.
| Tarceva 150 mg n=485 |
Placebo n=242 |
|||||
| NCI-CTC Grade | Any grade | Grade 3 | Grade 4 | Any grade | Grade 3 | Grade 4 |
| MedDRA preferred term | % | % | % | % | % | % |
| Rash | 75 | 8 | <1 | 17 | 0 | 0 |
| Diarrhea | 54 | 6 | <1 | 18 | <1 | 0 |
| Anorexia | 52 | 8 | 1 | 38 | 5 | <1 |
| Fatigue | 52 | 14 | 4 | 45 | 16 | 4 |
| Dyspnea | 41 | 17 | 11 | 35 | 15 | 11 |
| Cough | 33 | 4 | 0 | 29 | 2 | 0 |
| Nausea | 33 | 3 | 0 | 24 | 2 | 0 |
| Infection | 24 | 4 | 0 | 15 | 2 | 0 |
| Vomiting | 23 | 2 | <1 | 19 | 2 | 0 |
| Stomatitis | 17 | <1 | 0 | 3 | 0 | 0 |
| Pruritus | 13 | <1 | 0 | 5 | 0 | 0 |
| Dry Skin | 12 | 0 | 0 | 4 | 0 | 0 |
| Conjunctivitis | 12 | <1 | 0 | 2 | <1 | 0 |
| Keratoconjunctivitis sicca | 12 | 0 | 0 | 3 | 0 | 0 |
| Abdominal pain | 11 | 2 | <1 | 7 | 1 | <1 |
Please see ADVERSE REACTIONS section in the full prescribing information.
Q: What is the important safety information for Tarceva I should know?
A: There have been reports of serious Interstitial Lung Disease (ILD)-like events, including fatalities, in patients receiving Tarceva. In the NSCLC studies, the incidence of serious ILD-like events in the Tarceva treated patients versus placebo treated patients was 0.7% versus 0% in the maintenance study and 0.8% for both groups in the 2nd/3rd line study. The overall incidence of ILD-like events in approximately 32,000 Tarceva-treated patients from all studies (including uncontrolled studies and studies with concurrent chemotherapy) was approximately 1.1%.
Reported diagnoses in patients suspected of having ILD-like events included pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, ILD, obliterative bronchiolitis, pulmonary fibrosis, Acute Respiratory Distress Syndrome and lung infiltration. Symptoms started from 5 days to more than 9 months (median 39 days) after initiating Tarceva therapy.
Tarceva should be interrupted for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever. If ILD is diagnosed, Tarceva should be discontinued and appropriate treatment instituted as needed.
Cases of hepatorenal syndrome, acute renal failure (including fatalities), and renal insufficiency have been reported. Some were secondary to baseline hepatic impairment while others were associated with severe dehydration due to diarrhea, vomiting, and/or anorexia or concurrent chemotherapy use. In the event of dehydration, particularly in patients with contributing risk factors for renal failure (eg, pre-existing renal disease, medical conditions or medications that may lead to renal disease, or other predisposing conditions including advanced age), Tarceva therapy should be interrupted and appropriate measures should be taken to intensively rehydrate the patient. Periodic monitoring of renal function and serum electrolytes is recommended in patients at risk of dehydration.
Cases of hepatic failure and hepatorenal syndrome (including fatalities) have been reported during use of Tarceva, particularly in patients with baseline hepatic impairment. Therefore, periodic liver function testing (transaminases, bilirubin, and alkaline phosphatase) is recommended. In the setting of worsening liver function tests, dose interruption and/or dose reduction with frequent liver function test monitoring should be considered. Tarceva dosing should be interrupted or discontinued if total bilirubin is >3 x ULN and/or transaminases are >5 x ULN in the setting of normal pretreatment values.
Treatment with Tarceva should be used with extra caution in patients with total bilirubin > 3 x ULN. Patients with hepatic impairment (total bilirubin > ULN or Child-Pugh A, B and C) should be closely monitored during therapy with Tarceva. Tarceva dosing should be interrupted or discontinued if changes in liver function are severe such as doubling of total bilirubin and/or tripling of transaminases in the setting of pretreatment values outside normal range.
Gastrointestinal perforation (including fatalities) has been reported in patients receiving Tarceva. Patients receiving concomitant anti-angiogenic agents, corticosteroids, NSAIDs, and/or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease are at increased risk. Permanently discontinue Tarceva in patients who develop gastrointestinal perforation.
Bullous, blistering and exfoliative skin conditions have been reported including cases suggestive of Stevens-Johnson syndrome/toxic epidermal necrolysis, which in some cases were fatal. Interrupt or discontinue Tarceva treatment if the patient develops severe bullous, blistering or exfoliating conditions.
Corneal perforation and ulceration have been reported during use of Tarceva. Other ocular disorders including abnormal eyelash growth, keratoconjunctivitis sicca or keratitis have been observed with Tarceva treatment and are known risk factors for corneal ulceration/perforation. Interrupt or discontinue Tarceva therapy if patients present with acute/worsening ocular disorders such as eye pain.
International Normalized Ratio (INR) elevation and infrequent reports of bleeding events, including gastrointestinal and non-gastrointestinal bleeding, have been reported in clinical studies, some associated with concomitant warfarin administration. Patients taking warfarin or other coumarin-derivative anticoagulants should be monitored regularly for changes in prothrombin time or INR. Some infrequent cases of gastrointestinal bleeding were also associated with concomitant NSAID administration.
Tarceva is pregnancy category D. When receiving Tarceva, women of childbearing potential should be advised to avoid pregnancy and pregnant women apprised of the potential hazard to a fetus. Adequate contraception methods should be used during therapy, and for at least 2 weeks after completing therapy. Because of the potential for serious adverse reactions in nursing infants from Tarceva, a decision should be made whether to discontinue nursing or discontinue the drug.
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) and voriconazole, and grapefruit or grapefruit juice.
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.
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. 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.
Patients should be advised to stop smoking while taking Tarceva as cigarette smoking has been shown to reduce erlotinib AUC. However, if patients continue to smoke, a cautious increase in the dose of Tarceva, not to exceed 300 mg, may be considered while monitoring the patient's safety. If the Tarceva dose is adjusted upward, the dose should be reduced immediately to the indicated starting dose upon cessation of smoking.
The most common adverse reactions in patients with NSCLC receiving single-agent Tarceva 150 mg were rash and diarrhea. In the 2nd/3rd line study, severe rash and diarrhea (9% & 6% NCI-CTC Grades 3/4, respectively) were reported. Rash and diarrhea each resulted in dose reductions (6% and 1%, respectively) and discontinuation in 1% of Tarceva-treated patients. In the maintenance study, severe rash and diarrhea (6.0% & 1.8% NCI-CTC Grades 3/4, respectively) were reported. Rash and diarrhea resulted in dose reductions or interruption (5.1% and 2.8%, respectively) and discontinuation (1.2% and 0.5%, respectively) of Tarceva-treated patients.
Q: What is the recommended dosing for Tarceva?
A: The recommended once-daily dose of Tarceva for the treatment of NSCLC is 150 mg taken orally on an empty stomach.
Since food substantially increases the bioavailability of erlotinib and may increase the risk of adverse reactions, patients should be instructed to take Tarceva on an empty stomach at least one hour before or two hours after the ingestion of food.
The degree that food increases the bioavailability of erlotinib may vary; therefore, Tarceva tablets should be taken on an empty stomach to help ensure that patients obtain consistent plasma levels of the drug.
Administering Tarceva above 150 mg daily may result in an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation.
If the dose is missed, Tarceva can be taken at any time during the same day between meals. If the daily dose is missed entirely, the regularly prescribed dose should be taken the next day. Do not double the daily dose of Tarceva.
Treatment should continue until disease progression or unacceptable toxicity occurs; there is no evidence that treatment beyond disease progression is beneficial.
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