title: Phase II study of everolimus with biomarker exploration in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum.
abstract: BACKGROUND
  To evaluate the activity and safety of everolimus and identify potential biomarkers for efficacy of everolimus in patients with advanced gastric cancer (AGC), who failed both fluoropyrimidine and platinum.
  
  
  METHODS
  Fifty-four patients received everolimus (10 mg day(-1)). The primary objective was to determine the 4-month progression-free survival (PFS) rate, assumed to be 30%. We additionally investigated the potential biomarkers for everolimus as an exploratory endpoint in those who underwent tumour biopsies.
  
  
  RESULTS
  Two patients (3.7%) achieved partial response and the disease control rate (DCR) was 38.9%. At a median follow-up duration of 8.7 months, the 4-month PFS rate was 18.4%, not fulfilling the primary hypothesis, with a median PFS of 1.7 months and a median overall survival of 8.3 months. The high expression of pS6(Ser240/4) at baseline was significantly associated with higher DCR (P=0.043) and prolonged PFS (P=0.001). Grade 1/2 asthenia (96.3%) recorded as the leading toxicity and hyperglycaemia (20.4%) was the most common non-hematological grade 3/4 toxicity. Three patients experienced grade 3/4 pneumonitis. Notably, two experienced treatment-related deaths.
  
  
  CONCLUSIONS
  Everolimus is active against a limited number of patients with AGC. pS6(Ser240/4) may be a potential predictive biomarker for everolimus, which requires validation. Careful monitoring is necessary despite generally favourable toxicity profile.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: D H
authors.initials: DH
authors.lastname: Yoon
authors.forename: M-H
authors.initials: MH
authors.lastname: Ryu
authors.forename: Y S
authors.initials: YS
authors.lastname: Park
authors.forename: H J
authors.initials: HJ
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.forename: B-Y
authors.initials: BY
authors.lastname: Ryoo
authors.forename: J-L
authors.initials: JL
authors.lastname: Lee
authors.forename: H-M
authors.initials: HM
authors.lastname: Chang
authors.forename: T W
authors.initials: TW
authors.lastname: Kim
authors.forename: Y-K
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D017671:Platinum Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017671:Platinum Compounds; D000068338:Everolimus; D005472:Fluorouracil; D020123:Sirolimus