Enteral administration of TKIs: report of a response to ceritinib in an ALK-positive NSCLC patient and literature review.

Introduction: Several reports attest the feasibility and the favorable outcomes of kinase inhibitors administration through feeding tubes or Percutaneous Endoscopic Gastrostomies (PEG), mainly in Non-Small Cell Lung Cancer (NSCLC) patients exposed to first-generation compounds. Here we present the case of an ALK-positive NSCLC patient who achieved cerebral and extra-cranial disease response with ceritinib (a novel ALK inhibitor) administered through a Nasogastric Tube (NGT). We moreover provide a review gathering clinical successes obtained with targeted agents intake through NGT or PEG. Case Presentation: A 53-year-old never-smoker woman was diagnosed with ALK-rearranged stage IV lung adenocarcinoma. After a brilliant response to crizotinib and several lines of systemic therapy, NGT positioning intended for ceritinib administration was required, given the development of a pleuro-esophageal fistula. Enteral drug administration allowed a significant reduction of hepatic and cerebral disease localizations. Literature review and discussion: The majority of kinase inhibitors administration through NGT or PEG accounts for EGFR-mutated (seven) or ALK-positive (seven, including our report) NSCLC patients. Five additional cases concerning different malignancies were described. Enteral drug administration was mostly required by disease-related respiratory impairment, requiring mechanical ventilation in the emergency setting. In our case, the cerebral and extra-cranial response obtained with enteral ceritinib intake suggests the proposition of novel inhibitors in these circumstances may take place after first-generation compounds failure or even upfront. Indeed, their grater potency and activity against brain metastases point out the role of their enteral administration in the first-line setting too, when a rapid systemic and intra-cerebral disease response is required.