title: SWOG S0709: Randomized Phase II Trial of Erlotinib versus Erlotinib Plus Carboplatin/Paclitaxel in Patients with Advanced Non-Small Cell Lung Cancer and Impaired Performance Status as Selected by a Serum Proteomics Assay.
abstract: BACKGROUND
  Patients with advanced-stage non-small cell lung cancer (NSCLC) and borderline performance status (performance status 2 [PS2]) are often excluded from clinical trials and platinum-based therapy. In light of the potential role for serum proteomics in predicting the benefit of erlotinib beyond that of epidermal growth factor receptor gene (EGFR) mutational status, we conducted a trial in which the Veristrat proteomics assay was used for data enrichment when selecting a cohort of patients with NSCLC and PS2 to receive erlotinib with and without chemotherapy.
  
  
  METHODS
  Patients with metastatic NSCLC, PS2, acceptable end-organ function, and Veristrat-good status were randomly assigned to receive either 150 mg of erlotinib orally daily (arm 1) or 150 mg of erlotinib orally daily on days 2 through16 plus four cycles of carboplatin (area under the curve = 5 on day 1) and paclitaxel (200 mg/m(2) intravenously on day 1) followed by 150 mg of erlotinib orally (arm 2). The arm 2 agents were pharmacodynamically separated to mitigate potential antagonism. The arm with superior observed median progression-free survival (PFS) would be selected for further evaluation, but only if PFS lasted for at least 3 months.
  
  
  RESULTS
  The trial terminated before the planned accrual of 98 patients for regulatory reasons. A total of 156 patients were screened. Of the 83 (59%) who were classified as Veristrat good, 59 met the trial eligibility criteria and were randomly assigned to one of two arms (33 patients in arm 1 and 26 in arm 2). The patients in arm 2 patients had a higher response rate (23% versus 6%, p = 0.06), disease control rate (77% versus 41%, p = 0.0046), median PFS (4.6 versus 1.6 months, p = 0.06), and median overall survival (11 versus 6 months, p = 0.27). Treatment-related grade 4 adverse events were seen in two patients in arm 1 (thrombosis and hypomagnesemia) and in five patients in arm 2 (neutropenia in five, febrile neutropenia in one, and leukopenia in one).
  
  
  CONCLUSIONS
  In a proteomics-enriched cohort of patients with NSCLC and PS2, pharmacodynamically separated erlotinib plus chemotherapy had better efficacy than did erlotinib alone and surpassed the protocol-specified benchmark of PFS of at least 3 months required for further study.
authors.affiliation: University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA. Electronic address: pnlara@ucdavis.edu.
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.affiliation: Lahey Hospital and Medical Center, Burlington, MA, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hesketh
authors.affiliation: SWOG Statistical Center, Seattle, WA, USA.
authors.forename: Mary W
authors.initials: MW
authors.lastname: Redman
authors.affiliation: University of Kansas Cancer Center, Kansas City, KS, USA.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Williamson
authors.affiliation: University of Utah Medical Center, Salt Lake City, UT, USA.
authors.forename: Wallace L
authors.initials: WL
authors.lastname: Akerley
authors.affiliation: University of Colorado, Denver, CO, USA.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.affiliation: University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.affiliation: University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D040901:Proteomics
chemical_list: D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D017239:Paclitaxel