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Original Investigation
July 1, 2020

Evaluation of a Comprehensive Skin Toxicity Program for Patients Treated With Epidermal Growth Factor Receptor Inhibitors at a Cancer Treatment Center

Author Affiliations
  • 1Harvard Medical School, Boston, Massachusetts
  • 2Division of Dermatology, University of California, Los Angeles Medical Center, Santa Monica
  • 3Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 4Center for Cutaneous Oncology, Department of Dermatology, Dana-Farber/Brigham and Women’s Cancer Center, Boston, Massachusetts
JAMA Dermatol. Published online July 1, 2020. doi:10.1001/jamadermatol.2020.1795
Key Points

Question  What is the association of a comprehensive skin toxicity program with adherence to prophylaxis guidelines for the prevention of epidermal growth factor receptor inhibitor (EGFRi)–associated cutaneous toxic effects at a tertiary cancer center?

Findings  This cohort study of 208 patients with cancer treated with EGFRi found that adherence to prophylaxis protocols for cutaneous EGFRi-associated toxicity significantly improved over time and was associated with a decreased need for rescue treatments and a lower incidence of EGFRi dose changes, coinciding with the integration of dermatologic care into traditional oncology care.

Meaning  Integrating dermatologic care into oncology practices may be associated with increased adherence to evidence-based prophylaxis protocols for rash and may raise awareness of appropriate treatment choices, which may minimize toxicity-associated chemotherapy interruptions.


Importance  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.

Objective  To evaluate the association of a comprehensive skin toxicity program with adherence to prophylaxis guidelines for the prevention of EGFRi-associated cutaneous toxic effects.

Design, Setting, and Participants  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).

Main Outcomes and Measures  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.

Results  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 (P < .001). From 2012 to 2017, preemptive tetracycline use (13 of 29 [45%] to 30 of 42 [71%]; P = .02) and topical corticosteroid use (2 of 29 [7%] to 24 of 42 [57%]; P < .001) increased and topical antibiotic use (23 of 29 [79%] to 18 of 42 [43%]; P = .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; P < .001), 74% less likely to require a second rescue treatment for rash (adjusted odds ratio, 0.26; 95% CI, 0.08-0.83; P = .02), and 79% less likely to experience a cetuximab dose change or interruption (adjusted odds ratio, 0.21; 95% CI, 0.06-0.81; P = .02) than patients not prescribed prophylactic treatment, adjusting for treatment site and year.

Conclusions and Relevance  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.

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