Frequently Asked Questions
- Is there any head-to-head data between Tarceva (erlotinib) and chemotherapy in NSCLC?
- In which types of NSCLC patients is Tarceva use appropriate?
- What are Tarceva's indications?
- Should I use Tarceva in a particular patient type in NSCLC?
- Are there any potential drug interactions with Tarceva?
- Should I test my NSCLC patient's tumor tissue sample for EGFR expression or other markers?
- 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 are the important warnings and precautions with Tarceva?
- How do I dose Tarceva?
Q: Is there any head-to-head data between Tarceva (erlotinib) and chemotherapy in NSCLC?
A: There are no head-to-head studies on Tarceva vs chemotherapy.
Q: In which types of NSCLC patients is Tarceva use appropriate?
A:
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.
In the pivotal clinical trial for 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).
While Tarceva provides a proven survival benefit across a diverse patient population in the 2nd and 3rd line, retrospective analysis of BR.21 demonstrates that in the second-line setting, Tarceva provided a significant survival benefit for unselected patients, particularly those with good performance status (PS 0/1). In these PS 0/1 patients, Tarceva significantly increased overall survival by 47% vs placebo (HR=0.68; 95% CI=0.50-0.94; P=0.018), increased median survival by 40% (9.4 months vs 6.7 months) and increased 1-year survival by 33% (40% vs 30%).
To learn more about Tarceva safety information, please see Tarceva Safety Information and the FAQs about Tarceva common and serious adverse reactions included in this section.
Q: What are Tarceva's indications?
A:
Indication and Usage
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.
Indication and Usage
Tarceva in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
Q: Should I use Tarceva in a particular patient type in NSCLC?
A:
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 NSCLC pivotal trial (BR.21) showed an improvement in survival among an unselected population.
Some groups of patients appear to receive a greater survival benefit from Tarceva relative to the general population of patients with NSCLC in BR.21, such as patients who were nonsmokers and/or EGFR positive by IHC. The pivotal trial was not powered to analyze specific subsets prospectively; therefore, evidence-based treatment decisions should not be based solely on univariate analyses.
In BR.21, Tarceva benefited most patient populations, including: patients with squamous cell and adenocarcinoma, Caucasians and Asians, and smokers and nonsmokers.
Genentech, Inc., and OSI Pharmaceuticals, Inc., are actively engaged in additional studies designed to better understand the clinical relevance of disease characteristics and molecular markers to predict outcomes with Tarceva.
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) and voriconazole.
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 the co-treatment with rifampicin and CYP3A4 inducers such as, but not limited to: rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort.
Q: Should I test my NSCLC patient's tumor tissue sample for EGFR expression or other markers?
A: EGFR protein expression status was not a selection criterion for entry into the single-agent Phase III clinical trial. If tissue samples were available prior to study enrollment, they were examined retrospectively.
Genentech, Inc., and OSI Pharmaceuticals, Inc., are actively engaged in additional studies designed to better understand the clinical relevance of disease characteristics and molecular markers to predict outcomes with Tarceva.
Reports in the medical literature about the predictive value of EGFR mutations for a response to gefitinib should not be extrapolated to Tarceva. Some EGFR mutations have been shown to predict tumor shrinkage with Tarceva, but they may not be the best markers for the clinically meaningful endpoint of overall survival.
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 health care providers and their patients.
You can access Tarceva Access Solutions on the Internet at www.TarcevaAccessSolutions.com or call the toll-free support line at 1-888-249-4918.
If uninsured or financially challenged patients need help covering the cost of Tarceva, the experts at Genentech Access Solutions can help them with this issue.
The Genentech Access to Care Foundation was established to help qualified patients with unmet medical needs who are uninsured or rendered uninsured by payer denial and who meet specific medical criteria to receive proper medical treatment. The Genentech Access to Care Foundation may be available to help those who are not able to obtain Tarceva for financial reasons.
A: In the pivotal clinical trial for NSCLC, Grade 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. Based on the data that we have available from the pivotal trial, dose reduction did not appear to have an impact on overall survival.
The agents recommend by the NSCLC BR.21 protocol to manage rash included minocycline, topical tetracycline or clindamycin, topical silver sulfadiazine, dipenhydramine and oral prednisone. The efficacy of these agents was not assessed in the analysis of the BR.21 trial.
A: In the BR.21 NSCLC clinical trial, Grade 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 NSCLC pivotal trial, 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 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 a temporary interruption or dose reduction.
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
- then 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
Dose reduction is not appropriate if Interstitial Lung Disease (ILD), hepatic failure, or gastrointestinal perforations is diagnosed- Tarceva therapy should be discontinued. Interrupt or discontinue Tarceva in patients with dehydration who are at risk for renal failure, in patients with severe bullous, blistering or exfoliative skin conditions, or in patients with acute/worsening ocular disorders.
Q: What are the most common adverse reactions with Tarceva?
A: Tarceva has no known contraindications, and its safety profile has been established in more than 2,000 patients in completed clinical trials.
In the single-agent NSCLC Phase III trial, the most common side effects-rash and diarrhea-were generally mild to moderate. Each resulted in treatment discontinuation in 1% of Tarceva-treated patients.
| TARCEVA 150mg 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 |
Q: What are the important warnings and precautions with Tarceva?
A: There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events, including fatalities, in patients receiving Tarceva. The overall incidence of ILD-like events in Tarceva-treated patients from all studies was approximately 0.7%. In NSCLC, single agent Phase III study incidence was 0.8%-the same as placebo. In pancreatic cancer, in combination with gemcitabine study incidence was 2.5% in the Tarceva plus gemcitabine arm vs. 0.4% in the placebo plus gemcitabine arm.
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 the initiation of Tarceva therapy.
Tarceva should be interrupted for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever, and if ILD is diagnosed, Tarceva should be discontinued.
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.
When receiving Tarceva, women of childbearing potential should be advised to avoid pregnancy and pregnant women apprised of the potential risks to the fetus. Tarceva should only be continued in pregnant women if the potential benefit to the mother outweighs the risk to the fetus. Women receiving Tarceva should be advised against breastfeeding. Tarceva is pregnancy category D.
International Normalized Ratio (INR) elevation and infrequent reports of bleeding events, including 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.
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 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. 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 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. Co-administration of Tarceva with omeprazole, a proton pump inhibitor, decreased the erlotinib AUC by 46%. Increasing the dose of Tarceva when co-administered with such agents is not likely to compensate for the loss of exposure. The concomitant use of proton pump inhibitors with Tarceva should be avoided if possible.
Smokers should be advised to stop smoking while taking Tarceva as plasma concentrations of erlotinib are reduced due to the effect of cigarette smoking. However, if they continue to smoke, 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.
NCI-CTC Grade 3 conjunctivitis and keratitis have been reported infrequently in patients receiving Tarceva therapy. Corneal ulcerations may also occur.
The most common adverse reactions in patients with NSCLC receiving Tarceva monotherapy 150 mg were mild to moderate rash and diarrhea. 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 during the single-agent Phase III trial.
A: The recommended once-daily dose of Tarceva for the treatment of NSCLC is 150 mg taken orally.
Since food substantially increases the bioavailability of erlotinib and may increase the risk of adverse reactions, patients should be instructed to take Tarceva 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 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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