Phase II study of everolimus with biomarker exploration in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum

Br J Cancer. 2012 Mar 13;106(6):1039-44. doi: 10.1038/bjc.2012.47. Epub 2012 Feb 16.


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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm*
  • Everolimus
  • Female
  • Fluorouracil / pharmacology*
  • Fluorouracil / therapeutic use
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Patient Dropouts
  • Platinum Compounds / pharmacology*
  • Platinum Compounds / therapeutic use
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Platinum Compounds
  • Everolimus
  • Fluorouracil
  • Sirolimus