title: CALGB 30704 (Alliance): A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small-cell lung cancer.
abstract: BACKGROUND
  Second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) improves survival modestly but new strategies are needed. This trial was designed to evaluate an antivascular endothelial growth factor strategy with or without standard chemotherapy in previously treated NSCLC.
  
  
  METHODS
  Patients with stage IIIB/IV NSCLC with performance status 0 to 1 progressive after first-line chemotherapy were eligible for randomization to pemetrexed, sunitinib, or the combination. Patients were stratified by performance status, stage, and sex. Primary objective was 18-week progression-free survival (PFS) rate; secondary objectives included response, overall survival (OS), and toxicity. Target accrual was 225. The study was terminated early because of decreasing accrual rates.
  
  
  RESULTS
  Between April 2008 and September 2011, 130 patients were registered and randomized; of this, 125 patients were treated. Baseline characteristics in the three arms were well balanced. Toxicity was higher in the sunitinib-containing arms. The 18-week PFS rate in the pemetrexed, sunitinib, and combination arms was 54% (95% confidence interval [CI], 40-71), 37% (95% CI, 25-54), and 48% (95% CI, 35-66), respectively (p = 0.25). Median PFS in the pemetrexed, sunitinib, and combination arms in months was 4.9 (2.1-8.8), 3.3 (2.3-4.2), and 3.7 (2.5-5.8), respectively (p = 0.18). There was an overall statistically significant difference in OS between the three arms: median OS in months was 10.5 (8.3-20.2) for pemetrexed, 8.0 (6.8-13.5) for sunitinib, and 6.7 (4.1-10.1) for the combination (p = 0.03).
  
  
  CONCLUSIONS
  Pemetrexed had a superior toxicity profile to either sunitinib or the combination of pemetrexed and sunitinib. The 18-week PFS rate was not significantly different between the arms. OS was significantly better with pemetrexed alone compared with the two sunitinib-containing arms, with the doublet performing worst for OS.
authors.affiliation: *Department of Thoracic Oncology, Massachusetts General Hospital, Boston, Massachusetts; †Department of Oncology, Alliance Statistics and Data Center, Duke University Medical Center, Durham, North Carolina; ‡Department of Oncology, Ohio State University Medical Center, Columbus, Ohio; §Department of Oncology, University of North Carolina, Chapel Hill, North Carolina; ‖Department of Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; ¶Department of Oncology, Kinston Medical Specialists, P.A., Kinston, North Carolina; #Department of Oncology, University of Chicago, Chicago, Illinois; and **Department of Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Heist
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Lydia
authors.initials: L
authors.lastname: Hodgson
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.forename: Leena
authors.initials: L
authors.lastname: Gandhi
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Villalona-Calero
authors.forename: Peter
authors.initials: P
authors.lastname: Watson
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage; D012074:Remission Induction; D016879:Salvage Therapy; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D005971:Glutamates; D007211:Indoles; D011758:Pyrroles; D000068437:Pemetrexed; D006147:Guanine; D000077210:Sunitinib