title: Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study.
abstract: BACKGROUND
  Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice.
  
  
  METHODS
  Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB-IV); an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7.5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906.
  
  
  RESULTS
  At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade > or = 3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily interrupted after 28 (2%) of 1347 bleeding events and 72 (7%) of 1025 hypertension events, and permanently discontinued after 110 (8%) bleeding events and 40 (4%) hypertension events. No new safety signals were reported.
  
  
  CONCLUSIONS
  Our results confirm the manageable safety profile of first-line bevacizumab in combination with various standard chemotherapy regimens for treatment of advanced non-squamous NSCLC.
  
  
  BACKGROUND
  F Hoffmann-La Roche Ltd.
authors.affiliation: Department of Oncology, Hospital Santa Maria della Misericordia, Sant Andrea delle Fratte, Perugia, Italy. lcrino@unipg.it
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.forename: Eric
authors.initials: E
authors.lastname: Dansin
authors.forename: Pilar
authors.initials: P
authors.lastname: Garrido
authors.forename: Frank
authors.initials: F
authors.lastname: Griesinger
authors.forename: Janessa
authors.initials: J
authors.lastname: Laskin
authors.forename: Nick
authors.initials: N
authors.lastname: Pavlakis
authors.forename: Daniel
authors.initials: D
authors.lastname: Stroiakovski
authors.forename: Nick
authors.initials: N
authors.lastname: Thatcher
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Tsai
authors.forename: Yi-long
authors.initials: YL
authors.lastname: Wu
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab