Correlation between the severity of cetuximab-induced skin rash and clinical outcome for head and neck cancer patients: The XXXX experience

Publication date: Available online 26 March 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Voichita Bar-Ad, Qiang (Ed) Zhang, Paul M. Harari, Rita Axelrod, David I. Rosenthal, Andy Trotti, Christopher U. Jones, Adam S. Garden, Guobin Song, Robert L. Foote, David Raben, George Shenouda, Sharon A. Spencer, Jonathan Harris, Quynh-Thu Le
PurposeThe purpose of the present study was to evaluate severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy and cetuximab.Materials & MethodsAnalysis included patients who received loading dose and ≥ 1cetuximab dose concurrent with definitive chemoradiotherapy (70Gy + cisplatin) or postoperative chemoradiotherapy (60-66Gy + docetaxel or cisplatin).ResultsSix hundred two patients were analyzed; 383 (63.6%) developed Grade 2-4 cetuximab rash. Patients manifesting Grade 2-4 rash had younger age (p<0.001), fewer pack-years smoking history (p<0.001), were more likely to be males (p=0.04), and had p16-negative (p=0.04) oropharyngeal tumors (p=0.003).In univariate analysis, Grade 2-4 rash was associated with better overall survival (OS) (hazard ratio [HR] 0.58, p<0.001) and progression-free survival (PFS) (HR 0.75, p=0.02), and reduced distant metastasis (DM) rate (HR 0.61, p=0.03), but not local-regional failure (LRF) (HR 0.79, p=0.16) relative to Grade 0-1 rash. In multivariable analysis, HRs for OS, PFS, DM, and LRF were 0.68 (p=0.008), 0.85 (p=0.21), 0.64 (p=0.06), and 0.89 (p=0.48). Grade >2 rash was associated with improved survival in p16 negative patients (HR 0.28 (0.11-0.74)) but not in p16 positive patients (HR 1.10 (0.42-2.89)) (p=0.05 for interaction). Twenty-five percent of patients with Grade 2-4 acute in-field radiation dermatitis experienced Grade 2-4 late skin fibrosis vs. 14% of patients with Grade 0-1 acute in-field radiation dermatitis (p=0.002).ConclusionGrade 2-4 cetuximab rash was associated with better survival possibly due to reduction of distant metastasis. This observation was noted mainly in p16 negative patients. Grade 2-4 acute in-field radiation dermatitis was associated with higher rate of late Grade 2-4 skin fibrosis.

Teaser

Present study evaluated the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients HNSCC treated with chemoradiotherapy and cetuximab in two prospective randomized trials. Grade 2-4 cetuximab rash was associated with better survival possibly due to reduction of distant metastasis. This observation was noted mainly in p16 negative patients. Grade 2-4 acute in-field radiation dermatitis was associated with higher rate of late Grade 2-4 skin fibrosis.


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