Epidermal Growth Factor Receptor (EGFR) Inhibitor-Induced Rash: A Consecutive Patient Series that Illustrates the Need for Rigorous Palliative Trials

Abstract

Purpose: Rash is the most common side effect of epidermal growth factor receptor (EGFR) inhibitors and negatively impacts quality of life. This single-institution study sought to explore how rash is currently managed outside a clinical trial setting and to further characterize general clinical aspects of this rash. Methods/Results: Among 4101 consecutive patients with cancer of the lung, colorectum, pancreas, and head and neck, 138 had received an EGFR inhibitor. Within this group, 96 (69%) developed a rash. Forty-nine of these patients were prescribed rash therapy, and a total of 26 different palliative regimens were used. Surprisingly, most patients, with the exception of 2, appear to have manifested evidence of rash improvement-even when unproven or disproved therapies had been prescribed. Fourteen patients stopped their EGFR inhibitor because of rash, and 11 were then able to restart. No demographic variables were able to predict rash development. Conclusion: The observation that multiple, largely unproven, anecdotal therapies are being prescribed to palliate EGFR inhibitor-induced rashes underscores the need for more rigorous, prospective palliative trials.

Cutaneous Manifestations of EGFR-Inhibitors in African Americans and Treatment Considerations

“…argeted therapies in particular epidermal growth factor (EGFR)-inhibitors have emerged as the primary therapy in advanced solid tumor malignancies including colorectal, pancreas, head and neck cancers, and non-small cell lung carcinoma because of improvement in survival with overall favorable side effect profile. 1,2 EGFR-inhibitors include small molecule tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and lapatinib, as well as monoclonal antibodies such as cetuximab and panitumumab. 3,4,5 However, 50-90% of patients treated with EGFR-inhibitors develop a follicular or acneiform rash, which can be symptomatic and source of psychosocial distress, negatively impacting quality of life.…”

“…3,4,5 However, 50-90% of patients treated with EGFR-inhibitors develop a follicular or acneiform rash, which can be symptomatic and source of psychosocial distress, negatively impacting quality of life. 1,2,3 The pathogenesis of this rash is thought to be due to EGFR inhibition preventing keratinocyte migration, inducing keratinocyte apoptosis, and modulating cytokine release, which leads to the influx of inflammatory cells in the epidermis and dermis. 2,6 The epidermis becomes thin leading to skin atrophy and xerosis, and extensive follicular involvement can lead to scarring alopecia.…”

“…4 Areas with the highest follicle and sebaceous gland density, including the head and neck, chest, and back, are most frequently involved. 1,4 As this acneiform rash is a well-recognized cutaneous toxicity of EGFR-inhibitors, a treatment algorithm has been proposed for management based on severity. However, this algorithm does not account for biologic differences in skin in patients of different races and ethnicities.…”

Measuring symptoms as a critical component of drug development and evaluation in hematological diseases

“…Newer and more-intensive therapies have resulted in better disease control and the emergence of cancer as a chronic disease [24–28]. However, these newer therapies are sometimes associated with unexpected side effects that clinicians are not prepared to manage [29–33]. Furthermore, newer therapies are often administered orally and may require long-term use to control cancer.…”

Conducting Biobehavioral Research in Patients With Advanced Cancer: Recruitment Challenges and Solutions

“…Radiation therapy is associated with increased fatigue and uncomfortable skin reactions (Bray, Simmons, Wolfson, & Nouri, 2016). Targeted therapies such as those that inhibit the epidermal growth factor receptor (EGFR) can cause an itchy, painful rash (Lacouture et al, 2011; Solomon & Jatoi, 2011; Wickersham et al, 2014) and diarrhea. Finally, the stress response associated with living with cancer can lead to chronic activation of the hypothalamic–pituitary–adrenal and sympathetic–adrenal–medullary axes, ultimately leading to a dysfunctional inflammatory response and elevated anxiety, depression, and pain (Subnis, Starkweather, McCain, & Brown, 2014).…”