Tarceva Rash Information
Tarceva is a tyrosine kinase inhibitor.1
- In the EURTAC trial for first-line therapy in metastatic NSCLC with EGFR mutations (exon deletions or exon 21 [L858R] substitution mutations), rash occurred in 85% of patients in the Tarceva arm and 2% of patients in the chemotherapy arm; grade 3/4 rash was 14% in the Tarceva arm and 0% in the chemotherapy arm. Rash as a composite term included rash, acne, folliculitis, erythema, dermatitis acneiform, dermatitis, palmar-plantar erythrodysaesthesia syndrome, exfoliative rash, rash erythematous, rash pruritic, skin toxicity, eczema, rash follicular, and skin ulcer.1
- In the SATURN trial for maintenance therapy in locally advanced or metastatic NSCLC, rash occurred in 60% of patients in the Tarceva arm and 9% of patients in the placebo arm; grade 3/4 rash was 9% in the Tarceva arm and 0% in the placebo arm. Rash as a composite term included rash, acne, dermatitis acneiform, skin fissures, erythema, rash papular, rash generalized, rash pruritic, skin exfoliation, urticaria, dermatitis, eczema, exfoliative rash, dermatitis exfoliative, furuncle, rash macular, rash pustular, skin hyperpigmentation, skin reaction, and skin ulcer.1
- In the BR.21 trial for relapsed or refractory locally advanced or metastatic NSCLC, rash occurred in 75% of patients in the Tarceva arm and 17% of patients in the placebo arm; grade 3/4 rash was <9% in the Tarceva arm and 0% in the placebo arm. Rash as a composite term included rash, palmar-plantar erythrodysaesthesia syndrome, acne, skin disorder, pigmentation disorder, erythema, skin ulcer, dermatitis exfoliative, rash papular, and skin desquamation.1
Patient rash assessment
The algorithm and general rash management considerations featured here were developed by medical advisers at a company-sponsored advisory board meeting in October 2006. These recommendations were subsequently published.2 The medical advisers were paid by Genentech, Inc., OSI Pharmaceuticals, LLC (an affiliate of Astellas Pharma US, Inc.) and F. Hoffmann La Roche Ltd. to participate in the forum. Rash management information is included in the Tarceva Prescribing Information. However, other medical experts, including those at your institution, may have a different approach to managing rash.
*In advanced NSCLC trials, up to 1% of patients receiving Tarceva discontinued due to rash.1
Rash grading and sample rash management algorithm2
General rash management considerations
This algorithm has not been evaluated in a prospective manner for the management of Tarceva-related rash. The practices described below should not be construed as treatment recommendations; they must be interpreted with care and individualized for each patient.
- Employ a proactive approach to managing skin reactions2:
- For patients who present with rash2:
- Verify appropriate administration of Tarceva.2
Photos courtesy of Pamela Hallquist Viale, RN, MS, AOCNP.
Rash grading and rash management are subjective and may vary according to the judgment of the healthcare professional (HCP), as well as institutional guidelines and patients' symptoms. The grading methodology is not based on the NCI-CTC grading criteria. For patients in clinical trials, please follow adverse reactions grading, including rash criteria, per the trial's protocol.
The intervention information reflects the opinion of a select group of medical experts and should not be construed as evidence-based guidelines or as Genentech or Astellas recommendations. This information is not intended to serve as a substitute for independent medical judgment.
†Activities of daily living.‡
The use of these medications for the management of rash may be outside the FDA-labeled indications for these products. For complete information regarding the safety and use of these medications, please see the full Prescribing Information for each product.
§The use of topical steroids should be employed in a pulse manner based on your institution's guidelines.
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
- 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.
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.
- Tarceva [package insert]. Farmingdale, NY: OSI Pharmaceuticals, LLC, an affiliate of Astellas Pharma US, Inc.; 2013.
- Lynch TJ Jr, Kim ES, Eaby B, Garey J, West DP, Lacouture ME. Epidermal growth factor receptor inhibitor–associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist. 2007;12(5):610-621.
- Burtness B, Anadkat M, Basti S, et al. NCCN task force report: management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. J Natl Compr Canc Netw 2009;7(suppl 1):S5-S21.