EXPERT ANALYSIS FROM THE AAD SUMMER ACADEMY 2015
NEW YORK (FRONTLINE MEDICAL NEWS) – Due to the frequency with which patients develop pruritus while on a targeted cancer therapy, prophylaxis should be strongly considered for at least some of the drugs, such as epidermal growth factor–receptor (EGFR) inhibitors, according to an expert in oncodermatology.
“Pruritus is a frequent adverse event in cancer patients treated with targeted therapies and an early and proactive approach towards pruritus is advisable,” Dr. Mario E. Lacouture, director of the oncodermatology program at New York’s Memorial Sloan Kettering Cancer Center. The increasing use of targeted therapies, including the growing proportion of patients on long-term maintenance regimens, is expected to make these complaints more common.
Targeted cancer therapies, such as monoclonal antibodies and tyrosine kinase inhibitors (TKIs), are, in general, associated with a low risk of adverse events relative to cytotoxic chemotherapies. The exception is dermatologic adverse events, Dr. Lacouture said at the American Academy of Dermatology summer meeting. Skin rashes are characteristic adverse events with several targeted agents, such as the EGFR inhibitor cetuximab, but Dr. Lacouture warned that pruritus for many patients imposes the greatest burden.
“Since the introduction of the first targeted cancer drug, imatinib, in 2001, a long list of targeted agents have been approved, and all are associated with pruritus that significantly reduces quality of life,” he reported. Dermatologists need to fill a void.
“Oncologists are not generally familiar with strategies to treat pruritus and typically resort to antihistamines, such as diphenhydramine or hydroxyzine,” Dr. Lacouture added. He suggested such sedative agents “are not ideal” when managing an adverse event that may persist for weeks or months.
The first step may simply be to prepare patients initiating targeted therapy for the substantial risk of pruritus. Dr. Lacouture cited two studies in which cancer patients were asked about unexpected side effects. In both, dermatologic complaints were the most common.
“Patients are told that they are going to lose their hair, that they are going to have nausea and vomiting, but they are never told that they are going to have dry skin, irritated skin, or itchy skin,” Dr. Lacouture noted. He cited one study in which all three of the top side effects identified by cancer patients as unexpected were dermatologic, including nail changes and pruritus.
In fact, published studies suggest that most patients treated with EGFR inhibitors, and approximately one-third of patients treated with a variety of TKIs, such as those targeting BRAF and MEK pathways, will develop significant pruritus, according to Dr. Lacouture. However, several studies, including one of his own, suggest that this itching can be greatly mitigated not only by treatment but also with prophylaxis.
In his study of the effect of prophylaxis, 95 patients initiating the EGFR inhibitor panitumumab were randomized to a prophylactic regimen that included skin moisturizers, sunscreen, a topical steroid, and doxycycline, or to treatment adjusted for symptoms once they developed ( J Clin Oncol. 2010;28:1351-7 ). At 6 weeks, the proportion of patients with grade 2 or higher dermatologic events, including pruritus, was reduced from 62% to 29%. More favorable quality of life scores in the prophylactic regimen group supported the advantage.
“When you looked at grade 3 or higher adverse events, you see that the incidence of acneiform rash [at the grade 3 level of severity] was lowered by almost 75% and pruritus was almost abolished,” Dr. Lacouture reported.
For refractory pruritus related to targeted therapy, aprepitant may be the best option based on Dr. Lacouture’s own experience and a prospective but nonrandomized study ( Lancet Oncol. 2012;13:1020-4 ). In the published study, which included patients on EGFR inhibitors or TKIs, the median visual analog scores (VAS) for pruritus fell from 8 before treatment to 1, 1 week later. According to Dr. Lacouture, the treatment effects are durable. In some cases, pruritus does not recur even after a single course of aprepitant.
“The importance of pruritus in the cancer population is going to increase as targeted therapies enter the adjuvant setting,” Dr. Lacouture remarked. Also important, patients on targeted therapies are living longer, “and as patients live longer, more attention is being placed on quality of life issues of which pruritus is one of the topmost concerns.”
Dr. Lacouture reports financial relationships with Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Foamix, Galderma Laboratories, Hana Biosciences, Imclone, Merck Serono, Novartis, Novocure, OSI Pharma, Pfizer, Pierre Fabre Dermatologie, Reata Pharmaceuticals, Roche Laboratories, Threshold Pharmaceuticals, and Vertex Pharmaceuticals.