title: Clinical impact of switching to a second EGFR-TKI after a severe AE related to a first EGFR-TKI in EGFR-mutated NSCLC.
abstract: OBJECTIVE
  Somatic mutations in the epidermal growth factor receptor gene are associated with a therapeutic response to epidermal growth factor receptor tyrosine kinase inhibitors such as gefitinib and erlotinib in patients with non-small cell lung cancer. Although the safety profile of these drugs is favorable, a small proportion of patients with EGFR mutation-positive non-small cell lung cancer must discontinue treatment because of adverse events such as interstitial lung disease and hepatotoxicity. Subsequent chemotherapy has not been optimized in such patients.
  
  
  METHODS
  We performed a retrospective analysis of EGFR mutation-positive non-small cell lung cancer patients who received both gefitinib and erlotinib at our institution. Patients received the second epidermal growth factor receptor-tyrosine kinase inhibitor after experiencing an adverse event or progressive disease on the first epidermal growth factor receptor-tyrosine kinase inhibitor.
  
  
  RESULTS
  We identified 14 patients who received both gefitinib and erlotinib in the course of their treatment. Three patients initially treated with gefitinib and two with erlotinib discontinued epidermal growth factor receptor-tyrosine kinase inhibitor therapy because of severe non-hematologic toxicity (one because of gefitinib-induced interstitial lung disease, one because of erlotinib-induced lupus erythematosus-like eruption and three because of hepatotoxicity). All five of these patients were able successfully to continue therapy with the second epidermal growth factor receptor-tyrosine kinase inhibitor with no evidence of a recurrent adverse event. Progression-free survival was significantly longer in these five patients than in the nine patients who discontinued treatment with the first epidermal growth factor receptor-tyrosine kinase inhibitor because of disease progression.
  
  
  CONCLUSIONS
  EGFR mutation-positive non-small cell lung cancer patients who discontinue treatment with a first epidermal growth factor receptor-tyrosine kinase inhibitor because of an adverse event benefit substantially from switching to a second epidermal growth factor receptor-tyrosine kinase inhibitor before the development of drug resistance.
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, Japan. chi-okamoto@dotd.med.kindai.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.forename: Naoki
authors.initials: N
authors.lastname: Oiso
authors.forename: Akira
authors.initials: A
authors.lastname: Kawada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib