title: Phase 2 study of MK-2206, an allosteric inhibitor of AKT, as second-line therapy for advanced gastric and gastroesophageal junction cancer: A SWOG cooperative group trial (S1005).
abstract: BACKGROUND
  The AKT inhibitor MK-2206 at a dose of 60 mg every other day was evaluated in gastric/gastroesophageal junction cancers.
  
  
  METHODS
  Patients who had progressed after first-line treatment were eligible. Pertinent eligibility criteria included adequate organ function, a fasting serum glucose level ≤ 150 mg/dL, and less than grade 2 malabsorption or chronic diarrhea. MK-2206 was given orally (60 evaluable patients required). The primary endpoint was overall survival, and a median survival of 6.5 months (power, 89%; significance level, 0.07) was considered encouraging for further investigation.
  
  
  RESULTS
  Seventy patients were included in the final analyses. The median age was 59.8 years (range, 30.4-86.7 years); 70% were male, 89% were white, and 7% were Asian. There were 2 deaths possibly related to the study drug (cardiac arrest and respiratory failure). Grade 4 adverse events included hyperglycemia, anemia, and lung infection (1 each). Grade 3 adverse events occurred in < 5% of patients except for fatigue (6%). Other adverse events (all grades) included anemia (17%), anorexia (30%), diarrhea (26%), fatigue (50%), hyperglycemia (30%), nausea (40%), vomiting (22%), dry skin (19%), maculopapular rash (30%), and acneiform rash (13%). The response rate was 1%, the median progression-free survival was 1.8 months (95% confidence interval, 1.7-1.8 months), and the median overall survival was 5.1 months (95% confidence interval, 3.7-9.4 months)
  
  
  CONCLUSIONS
  MK-2206 as second-line therapy was well tolerated by an unselected group of patients with gastric/gastroesophageal junction cancers, but it did not have sufficient activity (response rate, 1%; overall survival, 5.1 months) to warrant further testing in this population.
authors.affiliation: Arizona Cancer Center, University of Arizona, Tucson, Arizona.|Virginia G. Piper Cancer Center, Scottsdale Healthcare, Scottsdale, Arizona.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.affiliation: Southwest Oncology Group Statistical Center, Seattle, Washington.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: McDonough
authors.affiliation: British Columbia Cancer Agency, Vancouver Centre, Vancouver, Canada.
authors.forename: Hagen F
authors.initials: HF
authors.lastname: Kennecke
authors.affiliation: USC Norris Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Syma
authors.initials: S
authors.lastname: Iqbal
authors.affiliation: University of Kansas Cancer Center, Westwood, Kansas.
authors.forename: Joaquina C
authors.initials: JC
authors.lastname: Baranda
authors.affiliation: Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, California.
authors.forename: Tara E
authors.initials: TE
authors.lastname: Seery
authors.affiliation: British Columbia Cancer Agency, Vancouver Centre, Vancouver, Canada.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York.
authors.forename: Aram F
authors.initials: AF
authors.lastname: Hezel
authors.affiliation: Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Vaccaro
authors.affiliation: British Columbia Cancer Agency, Vancouver Centre, Vancouver, Canada.|Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blanke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; C548887:MK 2206; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT inhibitor; MK-2206; gastric cancer; gastroesophageal junction; phase 2 study
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