A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group.
BACKGROUND
Accurate grading of dermatologic adverse events (AE) due to epidermal growth factor receptor (EGFR) inhibitors (EGFRIs) is necessary for drug toxicity determinations, interagent comparisons, and supportive care trials. The most widely used severity grading scale, the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0), was not designed specifically for this class of agents and may result in underreporting and poor grading of distinctive adverse events. We believe a class-specific grading scale is needed to help standardize assessment and improve reporting of EGFRI-associated dermatologic AEs.


METHODS
The Multinational Association of Supportive Care in Cancer (MASCC) Skin Toxicity Study Group conducted an international multidisciplinary meeting that included 20 clinicians and researchers from academic centers and government agencies. Experts from different disciplines presented current information specific to EGFRI-induced dermatologic toxicities: grading scale development, pharmacovigilance safety reporting, health-related quality of life, patient reporting, and pharmacology. Group discussions, literature reviews, and professional expertise established the theoretical foundation for the proposed grading scale.


RESULTS
A new grading system is proposed for the most common events associated with EGFRI-induced dermatologic AEs: papulopustular reaction or acneiform rash, nail changes, erythema, pruritus, xerosis, hair changes, telangiectasias, hyperpigmentation, mucositis, flushing, radiation dermatitis, hyposalivation, and taste changes. The proposed scale maintains consistency with the grading principles and language of the existing CTCAE version 4.0 and MedDRA terminology and includes relevant patient-reported health-related quality of life factors.


CONCLUSIONS
A grading scale specific to EGFR inhibitor dermatologic AEs is presented for formal integration into future versions of CTCAE and for validation in clinical trial settings. The study group designed this scale to detect and report EGFRI-related toxicities with greater sensitivity, specificity, and range than the scales currently used. This scale should serve as a foundation for efforts to perform objective interdrug comparisons and assessments of supportive care treatment strategies more effectively than with current methods.
Dermatology Service, Rockefeller Outpatient Pavilion, Memorial Sloan-Kettering 53rd Street, 160 East 53rd Street, New York, NY 10022, USA. LacoutuM@mskcc.org
Mario E
ME
Lacouture
Michael L
ML
Maitland
Siegfried
S
Segaert
Ann
A
Setser
Robert
R
Baran
Lindy P
LP
Fox
Joel B
JB
Epstein
Andrei
A
Barasch
Lawrence
L
Einhorn
Lynne
L
Wagner
Dennis P
DP
West
Bernardo L
BL
Rapoport
Mark G
MG
Kris
Ethan
E
Basch
Beth
B
Eaby
Sandra
S
Kurtin
Elise A
EA
Olsen
Alice
A
Chen
Janet E
JE
Dancey
Andy
A
Trotti
D000970:Antineoplastic Agents / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology / Q000503:physiopathology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D011788:Quality of Life; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D000970:Antineoplastic Agents; D066246:ErbB Receptors