EGFR Inhibitor-Associated Dermatologic Toxicities and Their Treatments

EGFR Inhibitor-Associated Dermatologic Toxicities and Their Treatments

A team of experts insight into supportive care prevention and treatment solutions for EGFRI-induced dermatologic toxicities.

Overexpression of the epidermal growth factor receptor (EGFR) is widely correlated with cancer development and the progression of a wide array of the state or presence of a malignant tumor. EGFR inhibitors (EGFRI) are targeted agents used for treating lung (erlotinib), pancreatic (erlotinib in combination with gemcitabine), breast (lapatinib in combination with capecitabine or anastrozole), head and neck (cetuximab in combination with radiotherapy), and colorectal cancers (cetuximab, panitumumab.) EGFRI inhibitors can be used as first-line through third-line treatments, singularly or in combination with other agents in the cancers mentioned previously.

Some of the most regularly experienced dermatologic side effects are included, but not limited to papulopustular changes in hair, like alopecia, for example, radiation dermatitis enhancement, pruritus, mucositis, xerosis or fissures, and paronychia. Incidences of these side effects are frequent and range from 36% for mucositis to 80% for a papulopustular rash.

While these indicators have been mentioned elsewhere, in previous medical texts, one important detail to note is that severe dermatologic toxicities can possibly lead to dose modification or discontinuation by 36% and 72% of health care providers. Although the side effect profile may be mainly dermatologic, toxicities cause significant discomfort, both emotionally and physically and therefore it is critical to have supportive measures and solutions in place for every patient that experiences these negative side effects.

While the majority of patients receiving EGFRI’s encounter these specific toxicities, determining the best practices for their solutions is difficult since very few actual clinical studies have been carried out. In fact, most of the research surrounding the effects and treatments for EDFRI’s only detail recommendations grounded in case reports or studies with miniature sample sizes and patient allocation that is often times nonrandomized.

Additionally, the reports that have been made publicly available are filled with methodological issues including, but not limited to, the failure to adequately describe assessment tools or their frequency, lack of validated tools for the assessment of dermatologic toxicities, and passive data collection. As a result of these previous reports being filled with so many errors and the limited range of their experiments, it is necessary, however, very unlikely that they will become available in the near future. One major reason for further investigation and research regarding the best supportive measures for EGFRI toxicities is the fact that these agents are, for the most part, devoid of hematopoietic and systemic toxicities and have also been shown to benefit in an array of solid tumors.

To resolve the issues and discrepancies, the Multinational Association for Supportive Care in Cancer formed an interdisciplinary group of international experts in dermatology, oncology, HQOL, and pharmacovigilance to conduct additional research and experience that can provide additional insight into information regarding the supportive care prevention and treatment solutions for EGFRI-induced dermatologic toxicities.

The medical panel of experts discovered that during the first weeks to months of EGFRI therapy, a papulopustular (acneiform) rash is the most clinically significant dermatologic toxicity. This particular rash is commonly developed in cosmetically sensitive dermatological areas, affecting the large majority of patients that have undergone treatment. Additionally, pruritic and tender erythematous papules and pustules develop in the skin with a high density of sebaceous glands (scalp, face, upper chest, and back).  After performing histological analysis, the panel also discovered that there is oftentimes a superficial inflammatory cell that infiltrates surrounds the hyperkeratotic or ectatic follicular infundibulum or a florid neutrophilic suppurative folliculitis with rupture of the epithelial lining.

This rash is entirely noteworthy for its harsh impact on a patient’s psychological well being, additional or secondary infections, and the intensity of a patient’s dosage with the patient’s emotions being the primary component in regards to the effect this rash has on their personal well being. Since common symptoms included pain, burning, and irritation, this often times led patients to experience extreme emotional stress. An additional survey of oncology practitioners revealed that 32% of providers did not continue therapy and that 76% modified the dose when the rash worsened or become more severe.