title: A randomized, double-blind, phase II study of erlotinib with or without sunitinib for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC).
abstract: Combined inhibition of vascular, platelet-derived, and epidermal growth factor receptor (EGFR) pathways may overcome refractoriness to single agents in platinum-pretreated non-small-cell lung cancer (NSCLC).
  
  
  
  This randomized, double-blind, multicenter, phase II trial evaluated sunitinib 37.5 mg/day plus erlotinib 150 mg/day versus placebo plus erlotinib continuously in 4-week cycles. Eligible patients had histologically confirmed stage IIIB or IV NSCLC previously treated with one or two chemotherapy regimens, including one platinum-based regimen. The primary end point was progression-free survival (PFS) by an independent central review.
  
  
  
  One hundred and thirty-two patients were randomly assigned, and the median duration of follow-up was 17.7 months. The median PFS was 2.8 versus 2.0 months for the combination versus erlotinib alone (HR 0.898, P = 0.321). The median overall survival (OS) was 8.2 versus 7.6 months (HR 1.066, P = 0.617). Objective response rates (ORRs) were 4.6% and 3.0%, respectively. Sunitinib plus erlotinib was fairly well tolerated although most treatment-related adverse events (AEs) were more frequent than with erlotinib alone: diarrhea (55% versus 33%), rash (41% versus 30%), fatigue (31% versus 25%), decreased appetite (30% versus 13%), nausea (28% versus 14%), and thrombocytopenia (13% versus 0%).
  
  
  
  The addition of sunitinib to erlotinib did not significantly improve PFS in patients with advanced, platinum-pretreated NSCLC.
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, Groningen, The Netherlands. h.j.m.groen@long.umcg.nl
authors.forename: H J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: M A
authors.initials: MA
authors.lastname: Socinski
authors.forename: F
authors.initials: F
authors.lastname: Grossi
authors.forename: E
authors.initials: E
authors.lastname: Juhasz
authors.forename: C
authors.initials: C
authors.lastname: Gridelli
authors.forename: P
authors.initials: P
authors.lastname: Baas
authors.forename: C A
authors.initials: CA
authors.lastname: Butts
authors.forename: E
authors.initials: E
authors.lastname: Chmielowska
authors.forename: T
authors.initials: T
authors.lastname: Usari
authors.forename: P
authors.initials: P
authors.lastname: Selaru
authors.forename: C
authors.initials: C
authors.lastname: Harmon
authors.forename: J A
authors.initials: JA
authors.lastname: Williams
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.forename: L
authors.initials: L
authors.lastname: Tye
authors.forename: R C
authors.initials: RC
authors.lastname: Chao
authors.forename: G R
authors.initials: GR
authors.lastname: Blumenschein
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077210:Sunitinib; D013534:Survival; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib
keywords: combination therapy; efficacy; erlotinib; non-small-cell lung cancer; safety; sunitinib