title: A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer.
abstract: OBJECTIVE
  Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated patients with non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m(2) ganetespib by intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until disease progression. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies.
  
  
  RESULTS
  Ninety-nine patients with a median of 2 prior systemic therapies were enrolled; 98 were assigned to cohort A (n = 15), B (n = 17), or C (n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively. Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n = 1) or PCR-based assays (n = 3), in crizotinib-naïve patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The most common AEs were diarrhea, fatigue, nausea, and anorexia.
  
  
  CONCLUSIONS
  Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA. socinskima@upmc.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goldman
authors.forename: Iman
authors.initials: I
authors.lastname: El-Hariry
authors.forename: Marianna
authors.initials: M
authors.lastname: Koczywas
authors.forename: Vojo
authors.initials: V
authors.lastname: Vukovic
authors.forename: Leora
authors.initials: L
authors.lastname: Horn
authors.forename: Eugene
authors.initials: E
authors.lastname: Paschold
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
authors.forename: Howard
authors.initials: H
authors.lastname: West
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
authors.forename: Julie
authors.initials: J
authors.lastname: Brahmer
authors.forename: Lin-Chi
authors.initials: LC
authors.lastname: Chen
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: Timothy
authors.initials: T
authors.lastname: Webb
authors.forename: Harry
authors.initials: H
authors.lastname: Harper
authors.forename: Mark
authors.initials: M
authors.lastname: Huberman
authors.forename: Suresh
authors.initials: S
authors.lastname: Ramalingam
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.forename: Florentina
authors.initials: F
authors.lastname: Teofilovici
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: Shapiro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement; D005838:Genotype; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; C533237:STA 9090; D014230:Triazoles; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
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