Rash Information

Rash

• Tarceva (erlotinib) is a HER1/EGFR tyrosine kinase inhibitor. HER1/EGFR is found in some types of tumor cells as well as on normal epidermal cells, such as those of the skin. Although the etiology is unknown, Tarceva has been associated with the development of rash.¹

Rash characteristics

• In BR.21 and PA.3, the pivotal clinical trials for Tarceva in advanced NSCLC and advanced pancreatic cancer, respectively, rash was among the most common side effects, reported in about 75% of patients with advanced NSCLC and about 69% of patients with advanced pancreatic cancer.^{1, 2}
• Tarceva-related rash was associated with 1% discontinuation in both pivotal clinical trials; 6% and 2% of Tarceva- treated patients required dose reductions in BR.21 and PA.3, respectively.¹
• Typically, the rash develops about 8 to 10 days after the start of treatment.^1,2 In general, rash may appear between 1 and 113 days.²
• Tarceva-related rash generally was mild to moderate and affected skin areas above the waist.^{2, 3}
• The occurrence of rash may be intermittent. Although rash is commonly referred to as "acneiform", it is not acne and should not be treated as acne.³

Patient rash assessment

Currently, there are no established guidelines in the dermatologic literature for the treatment of Tarceva-related skin reactions. The algorithm and general rash management considerations featured in the Rash grading and sample rash managment algorithm section should not be construed as Genentech or OSI recommendations, but rather were developed by medical advisors at a company-sponsored advisory board meeting in October 2006. These recommendations were subsequently published.⁴ The medical advisors were paid by Genentech, Inc., OSI Pharmaceuticals, Inc., and F. Hoffmann-La Roche Ltd. to participate in the forum. Other medical experts, including those at your institution, may have a different approach to managing rash.

* In an NSCLC trial and a pancreatic cancer trial, 1% of patients receiving Tarceva discontinued due to rash.

Rash grading and sample rash management algorithm^{* 4}

General rash management considerations

• Employ a proactive approach in managing skin reactions.
• Suggest patients use a thick, alcohol-free emollient cream on dry areas of the body.³
• Suggest patients use a sunscreen of SPF 15 or higher, preferably containing zinc oxide or titanium dioxide.^{3, 5}
• If patient presents with rash, verify appropriate administration and consider the following algorithm in a stepwise manner.

Rash grading is subjective and may vary according to the healthcare professional's judgment, institutional guidelines, and patient's symptoms. The above 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 above reflects the opinion of a select group of medical experts and should not be construed as evidence-based guidelines or as Genentech or OSI recommendations. This information is not intended to serve as a substitute for independent medical judgment.

*Algorithm developed by medical advisors at the Skin Toxicity Forum sponsored by Genentech, Inc., OSI Pharmaceuticals, Inc., and F. Hoffmann-La Roche Ltd. and held in Chicago, Illinois, in October 2006. The algorithm incorporates elements of other guidelines currently used in clinical practice, including those developed by Rhee et al and Lacouture et al.^6,7

**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.

†Activities of daily living.

††The use of topical steroids should be employed in a pulse manner based on your institution's guidelines.

Please also see:

• Dosing and Administration
• Adverse Reactions

• 1. Tarceva® [package insert]. Melville, NY: OSI Pharmaceuticals Inc; 2007.
• 2. Data on file, OSI Pharmaceuticals Inc.
• 3. Pèrez-Soler R, Delord JP, Halpern A, et al. HER1/EGFR inhibitor-associated rash: future directions for management and investigation outcomes from the HER1/EGFR Inhibitor Rash Management Forum. Oncologist. 2005;10(5):345-356.
• 4. 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.
• 5. National Cancer Institute. Chemotherapy and You: A Guide to Self-Help During Cancer Treatment. Bethesda, MD: National Cancer Institute, National Institutes of Health, US Department of Health and Human Services; 2003. NIH publication 03-1136.
• 6. Rhee J, Oishi K, Garey J, Kim E. Management of rash and other toxicities in patients treated with epidermal growth factor receptor-targeted agents. Clin Colorectal Cancer. 2005;5(suppl 2):S101-S106.
• 7. Lacouture ME, Basti S, Patel J, Benson A III. The SERIES clinic: an interdisciplinary approach to the management of toxicities of EGFR inhibitors. J Support Oncol. 2006;4(5):236-238.