title: A phase II study of erlotinib in combination with bevacizumab versus chemotherapy plus bevacizumab in the first-line treatment of advanced non-squamous non-small cell lung cancer.
abstract: BACKGROUND
  Molecularly targeted agents for non-small cell lung cancer (NSCLC) can provide similar efficacy to chemotherapy without chemotherapy-associated toxicities. Combining two agents with different modes of action could further increase the efficacy of these therapies. The TASK study evaluated the efficacy and safety of the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with the anti-angiogenic agent bevacizumab as first-line therapy in unselected, advanced non-squamous NSCLC patients.
  
  
  METHODS
  Patients were recruited from December 2007 to September 2008. Planned sample size was 200 patients, a total of 124 patients were randomized. Patients were randomized using a minimization algorithm 1:1 to receive bevacizumab (iv 15 mg/kg day 1 of each 21-day cycle) plus chemotherapy (gemcitabine/cisplatin or carboplatin/paclitaxel standard doses, 4-6 cycles) (BC arm) or bevacizumab plus erlotinib (p.o. 150 mg/day; BE arm) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). If the hazard ratio (HR) of PFS for BE relative to BC was above 1.25 at the pre-planned interim analysis in favor of BC, the study would be re-evaluated. Secondary endpoints included overall survival, response rate and safety.
  
  
  RESULTS
  All randomized patients (n = 63 BE; n = 61 BC) were evaluated for the efficacy analyses. At the updated interim analysis, median PFS was 18.4 weeks (95% confidence interval [CI] 17.0-25.1) versus 25.0 weeks (95% CI 20.6-[not reached]) for BE versus BC, respectively (HR for death or disease progression, BE relative to BC, 2.05, p = 0.0183). The incidence of death was 19% for BE treatment compared with 11.5% for BC treatment. The HR for PFS at the updated interim analysis was above 1.25, therefore patients on the BE arm were permitted to change arms or switch to another drug and the study was terminated. Adverse events reported were as expected.
  
  
  CONCLUSIONS
  The TASK study did not show a benefit in terms of PFS for the combination of erlotinib with bevacizumab in unselected first-line advanced non-squamous NSCLC compared with chemotherapy plus bevacizumab.
authors.affiliation: Institute of Oncology Ion Chiricuta, Cluj-Napoca, Romania; University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, 400015, Romania. Electronic address: tudor@iocn.ro.
authors.forename: T
authors.initials: T
authors.lastname: Ciuleanu
authors.forename: C-M
authors.initials: CM
authors.lastname: Tsai
authors.forename: C-J
authors.initials: CJ
authors.lastname: Tsao
authors.forename: J
authors.initials: J
authors.lastname: Milanowski
authors.forename: D
authors.initials: D
authors.lastname: Amoroso
authors.forename: D S
authors.initials: DS
authors.lastname: Heo
authors.forename: H J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: A
authors.initials: A
authors.lastname: Szczesna
authors.forename: C-Y
authors.initials: CY
authors.lastname: Chung
authors.forename: T-Y
authors.initials: TY
authors.lastname: Chao
authors.forename: G
authors.initials: G
authors.lastname: Middleton
authors.forename: A
authors.initials: A
authors.lastname: Zeaiter
authors.forename: G
authors.initials: G
authors.lastname: Klingelschmitt
authors.forename: B
authors.initials: B
authors.lastname: Klughammer
authors.forename: N
authors.initials: N
authors.lastname: Thatcher
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride
keywords: Bevacizumab; Combination therapy; Erlotinib; First-line; Non-small cell lung cancer; Non-squamous