Management of the Cutaneous Side Effects of Therapeutic Epidermal Growth Factor Receptor Inhibition

Abstract

The epidermal growth factor receptor (EGFR) is expressed in a variety of human tissues and is a key mediator of numerous cellular processes. Dysregulation and overexpression of the EGFR are common features of many tumors; targeted EGFR inhibitors are therefore widely employed as therapeutic agents. Novel mechanisms associated with EGFR inhibitors induce characteristic toxicities, of which cutaneous side effects (generally termed ‘skin rash’) are the most common. Although this rash is generally mild to moderate in severity, it can affect compliance and/or result in dose reductions or treatmentwithdrawal. To ensure that patients can continue to receive active treatment at the optimal dose, effective treatment strategies are required to actively manage rash and aid compliance. This is important as rash is increasingly identified as a predictive marker of benefit with EGFR inhibitors. The incidence and clinical characteristics of rash, in addition to current rash management strategies, are reviewed. Our recommendations based on clinical experience are presented, with two case studies of successful rash management provided to illustrate their success. Active rash management can effectively resolve rash to ensure that patient compliance is maintained, without necessitating dose interruptions or treatment withdrawal.

Treatment of Advanced Cutaneous Squamous Cell Carcinomas with Epidermal Growth Factor Receptor Inhibitors

“…The side effects that we saw in our patients and that were reported in the literature are similar to the side effects of EGFR inhibitors in indications other than cSCC and most frequently target the skin [11,27]. In two lung transplant recipients, diffuse alveolar damage was seen after one and three cetuximab infusions, pointing towards a possible unusual side effect in this particular patient subgroup [28].…”

Vandetanib for the Treatment of Thyroid Cancer

“…Overall, the prevalence of rashes of all types reached ~70% for all grades; rashes of CTCAE grade ≥2 were 20% in the first 3 months but remained at these levels over time, indicating that there was no cumulative toxicity 27 . In many cases, this rash was similar to that seen with other EGFR inhibitors, and there are several publications that provide guidance on the management of these rashes 28 , 29 . Toxic epidermal necrolysis, erythema multiforme, Stevens–Johnson syndrome, and toxic skin eruption have been reported as side effects in other vandetanib studies.…”

“…27 In many cases, this rash was similar to that seen with other EGFR inhibitors, and there are several publications that provide guidance on the management of these rashes. 28,29 Toxic epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome, and toxic skin eruption have been reported as side effects in other vandetanib studies. The treatment for severe skin reactions included systemic corticosteroids and either dose reduction or permanent discontinuation of vandetanib.…”

Cutaneous side effects of inhibitors of the RAS/RAF/MEK/ERK signalling pathway and their management

“…Currently, there is no treatment for the cutaneous side effects caused by EGFR or B‐RAF and MEK‐inhibitors that is based on controlled clinical trials. Therefore, they are usually treated empirically, based on qualitative evidence 25,26,43 …”

“…Based on the experience gained in the management of EGFR‐inhibitor‐induced exanthema, 43 the following diagnostic and treatment procedures should be considered:…”