Safety and efficacy of combining afatinib and whole-brain radiation therapy in treating brain metastases from EGFR-mutated NSCLC: a case report and literature review

Combining EGFR-tyrosine kinase inhibitors (TKIs) to whole brain radiation therapy (WBRT) has been shown to be more effective than EGFR-TKIs or WBRT alone in treating brain metastases (BMs) from EGFR-mutated Non Small-Cell Lung Cancer (NSCLC). However, despite the combination results well tolerated, EGFR-TKIs are often discontinued before WBRT, to reduce the risk of possible side effects, potentially resulting in reduced treatment efficacy and possible progression of intra- and extra-cranial disease. Afatinib, an irreversible inhibitor of EGFR-TK, has been shown to radiosensitize NSCLC in pre-clinical models and, compared to the other EGFR-TKIs, more efficiently penetrates the blood-brain barrier. However, nowadays, only two case reports describe the therapeutic efficiency and safety of combining afatinib with WBRT. Herein, we report on a 58-year-old woman patient with symptomatic BMs from NSLCL, treated with afatinib and concomitant WBRT, 30 Gy in 10 fractions. Treatment induced a remarkable and persistent radiological regression of BMs and the disappearance of neurological symptoms. However, the patient experienced severe skin toxicity of G3, corresponding to the irradiation area. Toxicity was successfully treated pharmacologically, and the patient did not experience any BMs-related symptoms for the next 10 months. She died of COVID-19-related respiratory failure. The association of afatinib with WBRT appears to be a successful strategy in the control of BMs from EGFR-mutated NSCLC. However, it should be considered that the combination could be responsible for serious dermatological toxicity.