title: Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).
abstract: OBJECTIVE
  Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study).
  
  
  METHODS
  Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0).
  
  
  RESULTS
  Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant.
  
  
  CONCLUSIONS
  The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence the efficacy of second-line platinum-based chemotherapy.
authors: Department of Respiratory Medicine, Tohoku University Hospital, Sendai.
authors: Eisaku
authors: E
authors: Miyauchi
authors: Department of Respiratory Medicine, Tohoku University Hospital, Sendai akinoue@idac.tohoku.ac.jp.
authors: Akira
authors: A
authors: Inoue
authors: Department of Respiratory Medicine, Saitama Medical University Internal Medical Center, Saitama.
authors: Kunihiko
authors: K
authors: Kobayashi
authors: Department of Respiratory Medicine, Miyagi Cancer Center, Miyagi.
authors: Makoto
authors: M
authors: Maemondo
authors: Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai.
authors: Shunichi
authors: S
authors: Sugawara
authors: First Department of Medicine, Hokkaido University School of Medicine, Sapporo.
authors: Satoshi
authors: S
authors: Oizumi
authors: Department of Medical Oncology, KKR Sapporo Medical Center, Sapporo.
authors: Hiroshi
authors: H
authors: Isobe
authors: Department of Pulmonary Medicine and Oncology, Graduate School, Nippon Medical School, Tokyo.
authors: Akihiko
authors: A
authors: Gemma
authors: Department of Medical Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata.
authors: Yasuo
authors: Y
authors: Saijo
authors: Bioscience Medical Research Center, Niigata University Medical & Dental Hospital, Niigata.
authors: Hirohisa
authors: H
authors: Yoshizawa
authors: Department of Respiratory Medicine, Saitama Medical University, Saitama.
authors: Koichi
authors: K
authors: Hagiwara
authors: Department of Respiratory Medicine, South Miyagi Medical Center, Miyagi, Japan.
authors: Toshihiro
authors: T
authors: Nukiwa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; 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; D017239:Paclitaxel / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D017384:Sequence Deletion; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel; D000077156:Gefitinib
keywords: EGFR; gefitinib; lung cancer; mutation; second line