Relationship between skin rash and outcome in non-small-cell lung cancer patients treated with anti-EGFR tyrosine kinase inhibitors: a literature-based meta-analysis of 24 trials

Lung Cancer. 2012 Oct;78(1):8-15. doi: 10.1016/j.lungcan.2012.06.009. Epub 2012 Jul 12.


Background: Dermatological toxicity, usually in the form of acneiform rash, is frequently observed in non-small-cell lung cancer (NSCLC) patients treated with anti-EGF receptor (EGFR) tyrosine kinase inhibitors (TKIs). The objective of this review was to assess the predictive value of skin rash for outcome in patients with NSCLC treated with erlotinib and gefitinib.

Methods: We searched PubMed for articles reporting a correlation of skin rash with survival, progression and response rate. In total, 349 prospective or retrospective studies presenting data regarding patient outcome and skin toxicity were screened. Hazard ratios (HRs) with 95% confidence intervals for progression and survival and risk ratios (RRs) for response rate were obtained from these publications and pooled in a meta-analysis.

Results: This meta-analysis included 24 publications (17 prospective trials and 7 retrospective case series). Skin rash was found to be an independent predictive factor for survival (HR: 0.30; p<0.00001) and progression (HR: 0.50; p<0.00001). In addition, patients who developed grade 2-4 rash were more likely to respond to treatment respect to patients with no rash (42% vs. 7%). The result for survival meta-analysis appears to be similar for gefitinib and erlotinib.

Conclusion: These results are noteworthy, because patients with severe skin rash may be reassured over treatment outcome Skin rash during treatment with anti-EGFR TKIs for NSCLC represents a significantly strong predictor of the efficacy in particular for patients with unknown EGFR mutation status.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / complications*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Exanthema / chemically induced*
  • Humans
  • Lung Neoplasms / complications*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Neoplasm Staging
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Treatment Outcome


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Receptors, Vascular Endothelial Growth Factor