title: Bevacizumab and erlotinib (BE) first-line therapy in advanced non-squamous non-small-cell lung cancer (NSCLC) (stage IIIB/IV) followed by platinum-based chemotherapy (CT) at disease progression: a multicenter phase II trial (SAKK 19/05).
abstract: OBJECTIVE
  This phase II trial aimed to evaluate feasibility and efficacy of a first-line combination of targeted therapies for advanced non-squamous NSCLC: bevacizumab (B) and erlotinib (E), followed by platinum-based CT at disease progression (PD).
  
  
  METHODS
  103 patients with advanced non-squamous NSCLC were treated with B (15 mg/kg day 1 of each 21-day cycle) and E (150 mg daily) until PD or unacceptable toxicity. Upon PD patients received 6 cycles of CT (cisplatin/carboplatin and gemcitabine). The primary endpoint was disease stabilization rate (DSR) after 12 weeks of BE treatment.
  
  
  RESULTS
  101 patients were evaluable. Under BE, DSR at week 12 was 54.5%. 73 patients had at least stable disease (SD), including 1 complete remission and 17 partial responses (PR). No unexpected toxicities were observed. Median time to progression (TTP) under BE was 4.1 months. 62 patients started CT; 35 received at least 4 cycles (6 PR, 32 SD). At a median follow-up of 36 months, median overall survival (OS) was 14.1 months.
  
  
  CONCLUSIONS
  First-line BE treatment followed by a fixed CT regimen at PD is feasible with acceptable toxicity and activity. In a non-squamous NSCLC population unselected for EGFR status, we found OS rates similar to standard CT.
authors.affiliation: Oncology Institute of Southern Switzerland, Switzerland. francesco.zappa@clinicaluganese.ch
authors.forename: Francesco
authors.initials: F
authors.lastname: Zappa
authors.forename: Cornelia
authors.initials: C
authors.lastname: Droege
authors.forename: Daniel
authors.initials: D
authors.lastname: Betticher
authors.forename: Roger
authors.initials: R
authors.lastname: von Moos
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.forename: Adrian
authors.initials: A
authors.lastname: Ochsenbein
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Oppliger Leibundgut
authors.forename: Patrizia
authors.initials: P
authors.lastname: Froesch
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahel
authors.forename: Thomas
authors.initials: T
authors.lastname: Hess
authors.forename: Daniel
authors.initials: D
authors.lastname: Rauch
authors.forename: Petra
authors.initials: P
authors.lastname: Schmid
authors.forename: Michael
authors.initials: M
authors.lastname: Mayer
authors.forename: Susanne
authors.initials: S
authors.lastname: Crowe
authors.forename: Peter
authors.initials: P
authors.lastname: Brauchli
authors.forename: Karin
authors.initials: K
authors.lastname: Ribi
authors.forename: Miklos
authors.initials: M
authors.lastname: Pless
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D000068258:Bevacizumab; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002945:Cisplatin