title: A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS).
abstract: Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150mg dose (E150).
  
  
  
  Patients with stage IIIB/IV NSCLC (current smokers who failed first-line platinum-based chemotherapy) were randomized to receive E150 or E300 until progression/death/unacceptable toxicity.
  
  
  
  progression-free survival (PFS). Secondary endpoints: overall survival (OS), disease control rate and safety.
  
  
  
  A total of 342 patients were screened; the intent-to-treat population comprised 159 E300 patients and 154 E150 patients. Median PFS was 7.0 versus 6.9 weeks with E300 versus E150, respectively (unstratified hazard ratio [HR]=1.05, 95% confidence interval [CI]: 0.83-1.33; unstratified log-rank P=0.671). Median OS was 6.8 months in both arms (unstratified HR=1.03, 95% CI: 0.80-1.32; unstratified log-rank P=0.846). Overall, 89.2% (E300 arm) and 84.4% (E150 arm) experienced ≥1 adverse event (AE) of any grade (44.3% and 37%, respectively, experienced grade ≥3 AEs); AEs of special interest were reported in 67.7% and 47.4% of patients, respectively. E300 resulted in higher mean plasma concentrations versus E150, however, this did not improve efficacy.
  
  
  
  Despite the difference in erlotinib exposure, there was no evidence of an incremental efficacy benefit of a higher erlotinib dose versus the standard dose in this population of highly active smokers.
authors: Netherlands Cancer Institute, Thoracic Oncology, Amsterdam, The Netherlands. Electronic address: EF.Smit@vumc.nl.
authors: Egbert F
authors: EF
authors: Smit
authors: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
authors: Yi-Long
authors: YL
authors: Wu
authors: Centre Francois Baclesse, Caen, France.
authors: Radj
authors: R
authors: Gervais
authors: Shanghai Pulmonary Hospital, Shanghai, China.
authors: Caicun
authors: C
authors: Zhou
authors: Vall d'Hebron University Hospital, Barcelona, Spain.
authors: Enriqueta
authors: E
authors: Felip
authors: Jiangsu Province Cancer Hospital, Nanjing, China.
authors: Jifeng
authors: J
authors: Feng
authors: Dr Suat Seren Chest Diseases and Surgery Hospital, Izmir, Turkey.
authors: Salih Zeki
authors: SZ
authors: Guclu
authors: Innere Klinik and Poliklinik Tumorforschung, West German Cancer Centre, Essen, Germany.
authors: Mathias
authors: M
authors: Hoiczyk
authors: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors: Elena
authors: E
authors: Dorokhova
authors: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors: Ulrich
authors: U
authors: Freudensprung
authors: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors: Susan
authors: S
authors: Grange
authors: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors: Pablo Diego
authors: PD
authors: Perez-Moreno
authors: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors: Lada
authors: L
authors: Mitchell
authors: LungenClinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.
authors: Martin
authors: M
authors: Reck
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011788:Quality of Life; D019233:Retreatment; D000074285:Smokers; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride
keywords: Erlotinib; Increased dose; NSCLC; Pharmacokinetics; Smoking