title: Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer.
abstract: BACKGROUND
  The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT).
  
  
  METHODS
  The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m2in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles.
  
  
  RESULTS
  The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL.
  
  
  CONCLUSIONS
  These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.
authors.affiliation: a Department of Immunology, Genetics and Pathology , Uppsala University , Uppsala , Sweden.|b Gävle Hospital, Center for Research & Development , Uppsala University/County Council of Gävleborg , Gävle , Sweden.|c Department of Radiation Sciences , Umeå University , Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Bergqvist
authors.affiliation: a Department of Immunology, Genetics and Pathology , Uppsala University , Uppsala , Sweden.|b Gävle Hospital, Center for Research & Development , Uppsala University/County Council of Gävleborg , Gävle , Sweden.
authors.forename: Georg
authors.initials: G
authors.lastname: Holgersson
authors.affiliation: d Dnipropetrovsk Medical Academy , City Multi-Field Clinical Hospital #4 , Dnipropetrovsk , Ukraine.
authors.forename: Igor
authors.initials: I
authors.lastname: Bondarenko
authors.affiliation: e PSI , St. Petersburg , Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Grechanaya
authors.affiliation: e PSI , St. Petersburg , Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Maximovich
authors.affiliation: f PSI , Budapest , Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Andor
authors.affiliation: g Axelar AB, Karolinska Institutet Science Park , Solna , Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Klockare
authors.affiliation: h Statisticon AB , Uppsala , Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Thureson
authors.affiliation: g Axelar AB, Karolinska Institutet Science Park , Solna , Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Jerling
authors.affiliation: g Axelar AB, Karolinska Institutet Science Park , Solna , Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Harmenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D043823:Taxoids; C415032:picropodophyllin; D000077143:Docetaxel; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin