Evaluation of a Comprehensive Skin Toxicity Program for Patients Treated With Epidermal Growth Factor Receptor Inhibitors at a Cancer Treatment Center
Authors: Zizi Yu, Edward Christopher Dee, Daniel Q. Bach, Arash Mostaghimi, Nicole R. LeBoeuf
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> Up to 90% of patients treated with an epidermal growth factor receptor inhibitor (EGFRi) experience cutaneous toxic effects that are negatively associated with quality of life and lead to treatment interruptions. The Skin Toxicity Evaluation Protocol With Panitumumab trial found reduced incidence of skin toxicity and quality of life impairment with preemptive use of doxycycline hyclate, topical corticosteroids, moisturizers, and sunscreen, demonstrating the benefit of prophylactic treatment for skin toxicity. <h3>Objective</h3> To evaluate the association of a comprehensive skin toxicity program with adherence to prophylaxis guidelines for the prevention of EGFRi-associated cutaneous toxic effects. <h3>Design, Setting, and Participants</h3> A retrospective cohort study was conducted of all adult patients receiving at least 1 dose of cetuximab at the Dana-Farber Cancer Institute in the calendar year 2012 (2 years after publication of the Skin Toxicity Evaluation Protocol With Panitumumab) or the calendar year 2017 (2 years after full implementation of the Skin Toxicities from Anticancer Therapies program). <h3>Main Outcomes and Measures</h3> Primary outcomes were rate of preemptive rash treatment and selection of preemptive agents. Secondary outcomes were incidence of rash, rates of rescue treatments, rates of cetuximab dose changes or interruptions, and overall survival at 2 years. <h3>Results</h3> There were 118 patients (85 men; median age, 62.4 years [range, 23.5-91.7 years]) treated with cetuximab in 2012 and 90 patients (70 men; median age, 62.5 years [range, 30.7-90.5 years]) treated with cetuximab in 2017; 11 patients (9%) in 2012 and 31 patients (34%) in 2017 were treated at Dana-Farber Cancer Institute affiliate sites. At cetuximab treatment initiation, 29 patients (25%) in 2012 and 42 patients (47%) in 2017 were prophylactically treated for skin toxicity (<i>P</i> &lt; .001). From 2012 to 2017, preemptive tetracycline use (13 of 29 [45%] to 30 of 42 [71%];<i>P</i> = .02) and topical corticosteroid use (2 of 29 [7%] to 24 of 42 [57%];<i>P</i> &lt; .001) increased and topical antibiotic use (23 of 29 [79%] to 18 of 42 [43%];<i>P</i> = .002) decreased. There was no significant difference in incidence of rash by prophylaxis status. Patients prescribed prophylactic treatment were 94% less likely to require a first rescue treatment for rash (adjusted odds ratio, 0.06; 95% CI, 0.02-0.16;<i>P</i> &lt; .001), 74% less likely to require a second rescue treatment for rash (adjusted odds ratio, 0.26; 95% CI, 0.08-0.83;<i>P</i> = .02), and 79% less likely to experience a cetuximab dose change or interruption (adjusted odds ratio, 0.21; 95% CI, 0.06-0.81;<i>P</i> = .02) than patients not prescribed prophylactic treatment, adjusting for treatment site and year. <h3>Conclusions and Relevance</h3> Dermatologists can add value to oncology care by raising awareness of appropriate treatment options and increasing adherence to evidence-based prophylaxis protocols for EGFRi-associated rash, which is associated with decreased interventions and toxicity-associated chemotherapy interruptions.