Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience

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

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18 Scopus citations

Abstract

Purpose To evaluate the 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 chemoradiation therapy and cetuximab. Methods and Materials Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin). Results Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and had p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002). Conclusion Grade 2 to 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 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.

Original languageEnglish (US)
Pages (from-to)1346-1354
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume95
Issue number5
DOIs
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Bar-Ad, V., Zhang, Q. E., Harari, P. M., Axelrod, R., Rosenthal, D. I., Trotti, A., Jones, C. U., Garden, A. S., Song, G., Foote, R. L., Raben, D., Shenouda, G., Spencer, S. A., Harris, J., & Le, Q. T. (2016). Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience. International Journal of Radiation Oncology Biology Physics, 95(5), 1346-1354. https://doi.org/10.1016/j.ijrobp.2016.03.011