title: A population-based review of the feasibility of platinum-based combination chemotherapy after tyrosine kinase inhibition in EGFR mutation positive non-small cell lung cancer patients with advanced disease.
abstract: BACKGROUND
  The IPASS trial demonstrated superior progression free survival for Asian, light/never smoking, advanced, pulmonary adenocarcinoma patients treated with first-line gefitinib compared to carboplatin/paclitaxel, of which 59% of those tested were epidermal growth factor receptor (EGFR) mutation positive. In IPASS 39% of gefitinib treated patients went on to receive platin based polychemotherapy. We hypothesized that in a population-based setting fewer patients receive second-line platin based chemotherapy than those enrolled in a clinical trial.
  
  
  METHODS
  The Iressa Alliance program provided standardized EGFR mutation testing and appropriate access to gefitinib to all patients in British Columbia with advanced, non squamous non small cell lung cancer (NSCLC). We retrospectively analyzed clinical, pathologic data and outcomes for all patients tested in this program between March 2010 and June 2011.
  
  
  RESULTS
  A total of 548 patients were referred for testing and 22% of patients were mutation positive. Baseline characteristics of mutation negative and mutation positive; median age 67/65, male 41%/31%, Asian 15%/51%, never smoker 21%/58%, stage IV 80%/91%. Median overall survival was 12 months in mutation negative patients and not yet reached in mutation positive (p<0.0001). In mutation positive patients 5% of patients had a complete response, 46% partial response, 34% stable disease, 6% progressive disease. Twenty percent of patients continued on gefitinib after radiographic progression and clinical stability. Sixty-one gefitinib treated patients progressed at the time of analysis; 10% of patients received further gefitinib only, 38% platinum based doublet, 8% other chemotherapy and 44% no further treatment. Performance status most strongly predicted for delivery of second line chemotherapy.
  
  
  CONCLUSIONS
  This North American population based study shows similar efficacy of gefitinib in mutation positive patients compared to the IPASS trial. Contrary to our hypothesis, delivery of second line chemotherapy was feasible in a significant proportion of gefitinib treated patients.
authors.affiliation: British Columbia Cancer Agency, Department of Medical Oncology, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6. Electronic address: cmariano@bccancer.bc.ca.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mariano
authors.affiliation: British Columbia Cancer Agency, Department of Pathology, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6.
authors.forename: Ian
authors.initials: I
authors.lastname: Bosdet
authors.affiliation: British Columbia Cancer Agency, Department of Pathology, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6.
authors.forename: Aly
authors.initials: A
authors.lastname: Karsan
authors.affiliation: British Columbia Cancer Agency, Department of Pathology, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6.
authors.forename: Diana
authors.initials: D
authors.lastname: Ionescu
authors.affiliation: British Columbia Cancer Agency, Department of Medical Oncology, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6.
authors.forename: Nevin
authors.initials: N
authors.lastname: Murray
authors.affiliation: British Columbia Cancer Agency, Department of Medical Oncology, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6.
authors.forename: Janessa J
authors.initials: JJ
authors.lastname: Laskin
authors.affiliation: Department of Statistics, University of British Columbia, Canada.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: British Columbia Cancer Agency, Department of Medical Oncology, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6.
authors.forename: Barbara
authors.initials: B
authors.lastname: Melosky
authors.affiliation: British Columbia Cancer Agency, Department of Medical Oncology, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sun
authors.affiliation: British Columbia Cancer Agency, Department of Medical Oncology, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Ho
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D017671:Platinum Compounds / Q000627:therapeutic use*; D044382:Population Groups; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D017671:Platinum Compounds; D011799:Quinazolines; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel; D000077156:Gefitinib
keywords: Chemotherapy; EGFR; Gefitinib; Population-based; Second-line; TKI