Management of human epidermal growth factor receptor inhibitors-related acneiform rash: A position paper based on the first Europe/USA Delphi consensus process

Z Apalla; A Freites-Martinez; K Grafanaki; A Ortiz-Brugues; V Nikolaou; D Fattore; P Sollena; S Deverapalli; S Babakoohi; A Galimont; N Kluger; M Beylot-Barry; C Larocca; C Iriarte; J Smith; I Tattersall; R Dodiuk-Gad; M Sauder; C Carrera; B Kwong; M Whitley; N Leboeuf; P Romano; M Starace; V Mateeva; J Riganti; J Hirner; A B Patel; C M Reyes-Habito; L Kraehenbuehl; M Kheterpal; M Fida; J Hassel; M Lacouture; V Sibaud

doi:10.1111/jdv.20391

Management of human epidermal growth factor receptor inhibitors-related acneiform rash: A position paper based on the first Europe/USA Delphi consensus process

J Eur Acad Dermatol Venereol. 2024 Oct 26. doi: 10.1111/jdv.20391. Online ahead of print.

Authors

Z Apalla¹, A Freites-Martinez², K Grafanaki³, A Ortiz-Brugues⁴, V Nikolaou⁵, D Fattore⁶, P Sollena⁷, S Deverapalli⁸, S Babakoohi⁹, A Galimont¹⁰, N Kluger¹¹, M Beylot-Barry¹², C Larocca¹³, C Iriarte¹⁴, J Smith¹⁵, I Tattersall¹⁶, R Dodiuk-Gad^{17

18

19}, M Sauder^{20

21}, C Carrera^{22

23}, B Kwong²⁴, M Whitley^{25

26}, N Leboeuf^{13

27

28}, P Romano²⁹, M Starace³⁰, V Mateeva³¹, J Riganti³², J Hirner³³, A B Patel³⁴, C M Reyes-Habito³⁵, L Kraehenbuehl³⁶, M Kheterpal²⁶, M Fida³⁷, J Hassel³⁸, M Lacouture³⁹, V Sibaud⁴

Affiliations

¹ Second Dermatology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.
² Dermatology Service, Hospital Ruber Juan Bravo, and Universidad Europea, Madrid, Spain.
³ Dermatology Department, Medical School of University of Patras, Rio, Greece.
⁴ Oncodermatology Department, Cancer University Institute, Toulouse Oncopole, Toulouse, France.
⁵ First Dermatology Department, National and Kapodistrian University of Athens, Athens, Greece.
⁶ Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
⁷ Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
⁸ Tufts Medical Center Department of Dermatology, Boston, Massachusetts, USA.
⁹ Atrium Health Levine Cancer Institute, Wake Forest School of Medicine, Charlotte, North Carolina, USA.
¹⁰ Dermatology Department, Bravis Hospital, Bergen op Zoom, The Netherlands.
¹¹ Department of Dermatology, Allergology and Venereology, University of Helsinki, Helsinki, Finland.
¹² Department of Dermatology, University of Bordeaux, Bordeaux, France.
¹³ Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹⁴ Department of Dermatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
¹⁵ UC Irvine School of Medicine, Irvine, California, USA.
¹⁶ Department of Dermatology, New York University, New York, USA.
¹⁷ Faculties of Medicine, Haifa, Israel.
¹⁸ University of Toronto, Toronto, Canada.
¹⁹ Dermatology Department, Emek Medical Center, Afula, Israel.
²⁰ Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
²¹ Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
²² Dermatology Department, Hospital Clinic and Fundació Clínic per la Recerca Biomèdica - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
²³ University of Barcelona, Barcelona, Spain.
²⁴ Department of Dermatology, Stanford University, Palo Alto, California, USA.
²⁵ Department of Dermatology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
²⁶ Department of Dermatology, Duke University School of Medicine, Durham, North Carolina, USA.
²⁷ Harvard Medical School, Boston, Massachusetts, USA.
²⁸ Center for Cutaneous Oncology, Department of Dermatology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
²⁹ Maria Concetta Pucci Romano, Azienda Ospedaliera S.Camillo-Forlanini, Roma, Italy.
³⁰ Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.
³¹ Department of Dermatology and Venereology, Medical University - Sofia, Sofia, Bulgaria.
³² Department of Dermatology, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
³³ Department of Dermatology, University of Missouri Health Care, Columbia, USA.
³⁴ Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
³⁵ Los Banos Doctors Hospital and Medical Center, Los Banos, Laguna, Philippines.
³⁶ Department of Dermatology, University Hospital Zurich (USZ), Zürich, Switzerland.
³⁷ Dermatology Department, University of Medicine of Tirana, Tirana, Albania.
³⁸ Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg (A Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany on behalf of the DECOG Committee Side Effects), Heidelberg University, Heidelberg, Germany.
³⁹ Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

PMID: 39460590
DOI: 10.1111/jdv.20391

Abstract

Background: There is a need for unified guidance in the management of acneiform rash induced by epidermal growth factor receptor inhibitors (EGFRi) among dermatologists.

Objective: To establish unified international guidelines for the management of acneiform rash caused by EGFR inhibitors, based on an experts' Delphi consensus.

Methods: The initiative was led by five members of the European Academy of Dermatology and Venereology Task Force 'Dermatology for Cancer Patients' who developed a questionnaire that was circulated to a group of 32 supportive oncodermatology experts in Europe, Canada, Argentina, the US States and Asia. The questionnaire consisted of 84 statements in total, regarding diagnosis and treatment of EGFRi-induced acneiform rash. Experts responded to an anonymous 5-point Likert scale survey. The coordinators collected the first-round responses that were checked for consensus (≥75% agreement in positive [agree or strongly agree] or in negative [disagree or strongly disagree] vote). The statements that did not reach strong consensus in the first round were revised, according to experts' feedback, for a second-round survey.

Results: Strong consensus was reached in 75/84 (89.3%) of the statements, whilst moderate consensus was achieved in 6/84 elements. Key points include consideration of low-dose isotretinoin for refractory grade II/III acneiform rash, use of topical steroid-sparing agents like topical pimecrolimus in the maintenance phase and use of doxycycline in either 100 or 200 mg per day as prophylactic treatment. Interestingly, experts did not recommend topical antibiotics, neither for prevention, nor for treatment. Consensus failure in 3/84 objects is mostly related to the lack of robust data on these topics.

Conclusion: This consensus offers crucial insights often overlooked by radiotherapists, general practitioners, dermatologists and oncologists, and it is expected to improve the management of oncologic patients treated with EGFRi in different settings and continents.