Frequently Asked Questions
- What are Tarceva's indications?
- Should I use Tarceva in a particular patient type in pancreatic cancer?
- Are there any potential drug interactions with Tarceva?
- Are there insurance information resources available for Tarceva?
- 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: What are Tarceva's indications?
A:
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.
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.
Q: Should I use Tarceva in a particular patient type in pancreatic cancer?
A: The survival benefit of Tarceva plus gemcitabine was observed across most patient populations analyzed, as evidenced by hazard ratios ≤1.
Genentech, Inc., and OSI Pharmaceuticals, Inc., are actively evaluating whether there are any prognostic or predictive markers for Tarceva. See full prescribing information.
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: 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.
Q: What if my patient needs a dose reduction?
A: In the Tarceva plus gemcitabine pivotal trial, 87% of patients tolerated the 100-mg dose. Dose reductions occurred in 13% of patients. Rash and diarrhea each resulted in dose reductions in 2% of patients, respectively.
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 dose reduction or temporary interruption of Tarceva therapy. The pivotal Phase III protocol specified the following dose-modification guidelines for Grade ≤3 rash, diarrhea or other toxicities 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 or interruption of Tarceva should be considered in situations such as:
- intolerable skin reactions
- intolerable diarrhea that is unresponsive to loperamide or that causes dehydration
- severe liver function test abnormalities
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.
Gemcitabine dose administration could be withheld or reduced for toxicities following the recommendations in the manufacturer's package insert.
Q: What are the most common adverse reactions with Tarceva?
- Tarceva has no known contraindications, and its safety profile has been established in more than 2,000 patients in completed clinical trials.
- In the Phase III trial in combination with gemcitabine, the most common side effects, fatigue, rash, diarrhea, anorexia and nausea, were mild to moderate; rash and diarrhea each resulted in treatment discontinuation in up to 1% of patients receiving Tarceva plus gemcitabine.
- The incidence of fatigue in the Tarceva plus gemcitabine group was comparable to that in the placebo plus gemcitabine group.
- Severe rash and diarrhea (Grade 3/4) were each reported in 5% of patients who received Tarceva plus gemcitabine; each resulted in study discontinuation in 1% of patients.
| TARCEVA +
gemcitabine 1000 mg/m2 IV N=259 |
Placebo +
gemcitabine 1000 mg/m2 IV N=256 |
|||||
| NCI-CTC Grade | Any grade | Grade 3 | Grade 4 | Any grade | Grade 3 | Grade 4 |
| MedDRA Preferred Term | % | % | % | % | % | % |
| Fatigue | 73 | 14 | 2 | 70 | 13 | 2 |
| Rash | 69 | 5 | 0 | 30 | 1 | 0 |
| Nausea | 60 | 7 | 0 | 58 | 7 | 0 |
| Anorexia | 52 | 6 | <1 | 52 | 5 | <1 |
| Diarrhea | 48 | 5 | <1 | 36 | 2 | 0 |
| Abdominal pain | 46 | 9 | <1 | 45 | 12 | <1 |
| Vomiting | 42 | 7 | <1 | 41 | 4 | <1 |
| Weight decreased | 39 | 2 | 0 | 29 | <1 | 0 |
| Infection* | 39 | 13 | 3 | 30 | 9 | 2 |
| Edema | 37 | 3 | <1 | 36 | 2 | <1 |
| Pyrexia | 36 | 3 | 0 | 30 | 4 | 0 |
| Constipation | 31 | 3 | 1 | 34 | 5 | 1 | Bone pain | 25 | 4 | <1 | 23 | 2 | 0 |
| Dyspnea | 24 | 5 | <1 | 23 | 5 | 0 |
| Stomatitis | 22 | <1 | 0 | 12 | 0 | 0 |
| Myalgia | 21 | 1 | 0 | 20 | <1 | 0 |
| Depression | 19 | 2 | 0 | 14 | <1 | 0 |
| Dyspepsia | 17 | <1 | 0 | 13 | <1 | 0 |
| Cough | 16 | 0 | 0 | 11 | 0 | 0 |
| Dizziness | 15 | <1 | 0 | 13 | 0 | <1 |
| Headache | 15 | <1 | 0 | 10 | 0 | 0 |
| Insomnia | 15 | <1 | 0 | 16 | <1 | 0 |
| Alopecia | 14 | 0 | 0 | 11 | 0 | 0 |
| Anxiety | 13 | 1 | 0 | 11 | <1 | 0 |
| Neuropathy | 13 | 1 | <1 | 10 | <1 | 0 |
| Flatulence | 13 | 0 | 0 | 9 | <1 | 0 |
| Rigors | 12 | 0 | 0 | 9 | 0 | 0 |
| * Includes all MedDRA preferred terms in the Infections and Infestations System Organ Class. | ||||||
Please see ADVERSE REACTIONS section in the full package insert.
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.
In the pancreatic cancer trial, myocardial infarction/ischemia occurred in 2.3% of patients (6 patients) in the Tarceva plus gemcitabine arm vs. 1.2% (3 patients) in the placebo plus gemcitabine arm. One patient in the Tarceva plus gemcitabine arm and one patient in the placebo plus gemcitabine arm died due to myocardial infarction.
In the pancreatic cancer trial, 2.3% of patients (6 patients) in the Tarceva plus gemcitabine arm developed cerebrovascular accidents vs. no cerebrovascular accidents in the placebo plus gemcitabine arm. One of the cerebrovascular accidents was hemorrhagic and fatal.
In the pancreatic cancer trial, 0.8% of patients (2 patients) developed microangiopathic hemolytic anemia with thrombocytopenia in the Tarceva plus gemcitabine arm vs. no cases in the placebo plus gemcitabine arm.
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 pancreatic cancer receiving Tarceva 100 mg plus gemcitabine were fatigue, rash, nausea, anorexia and diarrhea. Severe rash and diarrhea (5% and 5% NCI-CTC Grades 3-4, respectively) were reported. Rash and diarrhea each resulted in dose reductions in 2% of patients, and discontinuation in up to 1% of patients receiving Tarceva plus gemcitabine.
A: The recommended once-daily dose of Tarceva for the treatment of pancreatic cancer is 100 mg* taken orally in combination with gemcitabine.
Tarceva is indicated for use in advanced pancreatic cancer in combination with gemcitabine1,000 mg/m2 IV. In the Phase III trial, patients received the approved gemcitabine dose and schedule for pancreatic cancer:
- Cycle 1 of gemcitabine: Days 1, 8, 15, 22, 29, 36 and 43 of an 8-week cycle
- Cycle 2 and subsequent cycles of gemcitabine: Days 1, 8 and 15 of a 4-week cycle
- Treatment should continue until disease progression or unacceptable toxicity occurs; there is no evidence that treatment beyond disease progression is beneficial.
- Patients should be instructed to take Tarceva at least one hour before or two hours after the ingestion of food, since food substantially alters the bioavailability of erlotinib and may increase the risk of adverse reactions. Tarceva tablets should be taken on an empty stomach to help ensure that patients obtain consistent plasma levels of the drug.
- If a 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, one hour before or two hours after a meal.
- Caution your patients not to double the daily prescribed dose of Tarceva. Administering Tarceva above the recommended daily dose may result in an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation.
*100 mg is the approved dose for the use of Tarceva in combination with gemcitabine for patients with pancreatic cancer; 150 mg is not recommended in this setting. In accordance with the clinical trial protocol, patients who were initially enrolled received a 100-mg dose of Tarceva or placebo. After the tolerability of the 100-mg dose level was established, patients were enrolled at the 150-mg dose level. However, only 48 patients (8% N = 569) were accrued in the 150-mg cohort before the target enrollment was reached; therefore, safety and efficacy were determined at the 100-mg dose level.
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