DIFFERENTIAL EFFECTS OF EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITORS IN A SINGLE CASE OF NEUROPATHIC PAIN
Marte Cameron MD PhD, Christian Kersten MD PhD
Sørlandet Hospital Trust, Kristiansand, Norway
Contact: marte.cameron@sshf.no 
Background: The human epidermal growth factor (HER) family of receptors consists of four members, including the epidermal growth factor receptor (EGFR, HER1). Both tyrosine kinase inhibitors (TKIs) and monoclonal antibodies inhibit HER receptors in oncology practice.  Neuropathic pain (NP) represents an unmet medical need, where analgesic responses to different EGFR-inhibitors (EGFR-I) have been described in patients.  This has appeared to be a class effect of EGFR-Is.1-5 
 Method: The clinical course of a single case of NP treated with 5 different EGFR-Is is described. 
Results: A 52 year-old male was included in a randomized, double-blind, cross-over proof of concept clinical trial testing cetuximab in chronic, treatment-refractory severe NP due to nerve compression.1  His NP scores decreased dramatically after blinded intravenous cetuximab, but not after placebo.  Therefore, upon pain recurrence after the trial, he was treated (off-label) with the oral TKIs erlotinib and gefitinib, but without NP relief. The oral pan-HER-inhibitor afatinib was then prescribed, with gradual NP improvement starting on day 4.  The patient was also given a trial of the oral HER1/HER2 TKI lapatinib, but reverted to afatinib after 7 days without pain relief.  Currently, after 2,5 years on afatinib (25mg/d), pain control is excellent (NRS 0-1/10) with only transient side effects (grade 1 mucositis and diarrhea).
Conclusion: This is the first report describing NP relief with afatinib and the first reported observation of differential effects of various EGFR-Is on NP in the same patient.  Further understanding of the pathophysiology may lead to development of EGFR-Is specifically targeting NP.