title: Multicenter phase II study of the AKT inhibitor MK-2206 in recurrent or metastatic nasopharyngeal carcinoma from patients in the mayo phase II consortium and the cancer therapeutics research group (MC1079).
abstract: BACKGROUND
  This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was measured, and archived tumors were analyzed for the expression of AKT and PIK3CA mutation and PIK3CA amplification. The dual primary endpoint was objective response rate and 6-month progression-free survival (PFS) rate.
  
  
  RESULTS
  21 patients were enrolled and one patient achieved a partial response (5 %) and 11 had stable disease (52 %), with a median PFS of 3.5 months (95 % confidence interval, CI: 0.9-7.3). The 6-month PFS rate was 43 % (95 % CI: 22-66 %) and the median OS was 10 months (95 % CI: 5.9 months-not reached). Seven patients (33 %) experienced grade 3 toxicities which could be related to MK-2206. Macular-papular rash was the most common (n = 6), followed by hyperglycemia (n = 2) and fatigue (n = 1). In the 12 tumor samples analyzed, PIK3CA amplification was detected in one patient's primary NPC, who had SD lasting over 12 months. Patients with decreasing EBV DNA values over time were more likely to be alive and progression-free for at least 6 months than those without a decrease (p = 0.001).
  
  
  CONCLUSIONS
  The study was terminated due to the limited activity observed in this heavily pre-treated group of patients. Further studies are needed to elucidate the optimal way of selecting patients for AKT inhibitors.
authors.affiliation: State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, Hong Kong SAR, brigette@clo.cuhk.edu.hk.
authors.forename: B B Y
authors.initials: BB
authors.lastname: Ma
authors.forename: B C
authors.initials: BC
authors.lastname: Goh
authors.forename: W T
authors.initials: WT
authors.lastname: Lim
authors.forename: E P
authors.initials: EP
authors.lastname: Hui
authors.forename: E H
authors.initials: EH
authors.lastname: Tan
authors.forename: G de Lima
authors.initials: Gde L
authors.lastname: Lopes
authors.forename: K W
authors.initials: KW
authors.lastname: Lo
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Loong
authors.forename: N R
authors.initials: NR
authors.lastname: Foster
authors.forename: C
authors.initials: C
authors.lastname: Erlichman
authors.forename: A D
authors.initials: AD
authors.lastname: King
authors.forename: M K M
authors.initials: MK
authors.lastname: Kam
authors.forename: S F
authors.initials: SF
authors.lastname: Leung
authors.forename: K C
authors.initials: KC
authors.lastname: Chan
authors.forename: A T C
authors.initials: AT
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma; D004279:DNA, Viral / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006575:Heterocyclic Compounds, 3-Ring / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004279:DNA, Viral; D006575:Heterocyclic Compounds, 3-Ring; C548887:MK 2206; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt