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

D. H. Yoon, M. H. Ryu, Y. S. Park, H. J. Lee, C. Lee, B. Y. Ryoo, J. L. Lee, H. M. Chang, T. W. Kim, Y. K. Kang

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

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. 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.

Original languageEnglish (US)
Pages (from-to)1039-1044
Number of pages6
JournalBritish Journal of Cancer
Volume106
Issue number6
DOIs
StatePublished - Mar 13 2012

Bibliographical note

Funding Information:
This study was supported, in part, by Novartis.

Keywords

  • advanced gastric cancer
  • biomarker
  • everolimus

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