title: A phase II trial of a selective c-Met inhibitor tivantinib (ARQ 197) monotherapy as a second- or third-line therapy in the patients with metastatic gastric cancer.
abstract: BACKGROUND
  Tivantinib is a selective, non-ATP competitive, small-molecule inhibitor of c-Met and is under development in several cancers including non-small cell lung and hepatocellular carcinoma. Activation of c-Met has been frequently found in metastatic gastric cancer (MGC) and is associated with poor prognosis. In this single-arm study, we evaluated the efficacy of tivantinib monotherapy in Asian patients with previously treated MGC. This is the first clinical report from the trials evaluating the efficacy of a selective c-Met inhibitor for MGC.
  
  
  METHODS
  Eligibility criteria included: MGC with at least one measurable lesion; 1 or 2 prior chemotherapy regimens; and ECOG PS 0 or 1. Tivantinib was daily administered orally. The primary endpoint was the disease control rate (DCR). Pre-treatment tumor tissue was collected to evaluate the biomarkers related to efficacy.
  
  
  RESULTS
  Thirty patients, including 12 patients with prior gastrectomy, received tivantinib: median age 62.5 years; ECOG PS 0/1 (8/22); 1/2 prior regimen (16/14). No objective response was observed, and DCR was 36.7 %. Median progression-free survival was 43 days (95 % CI: 29.0-92.0). Grade 3 or 4 adverse events occurred in 13 patients (43.3 %), in whom neutropenia (N = 4) and anemia (N = 4) were recognized as drug-related. c-Met gene amplification was observed in 2 patients (6.9 %). No obvious relationship was identified between efficacy and biomarkers including gene amplification of c-Met, expression of c-Met, p-Met and HGF.
  
  
  CONCLUSIONS
  Tivantinib as a monotherapy showed a modest efficacy in previously treated MGC, and further studies taking account of predictive biomarkers and/or combination with other chemotherapy may be needed in MGC.
authors: Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea, ykkang@amc.seoul.kr.
authors: Yoon-Koo
authors: YK
authors: Kang
authors: Kei
authors: K
authors: Muro
authors: Min-Hee
authors: MH
authors: Ryu
authors: Hirofumi
authors: H
authors: Yasui
authors: Tomohiro
authors: T
authors: Nishina
authors: Baek-Yeol
authors: BY
authors: Ryoo
authors: Yukimasa
authors: Y
authors: Kamiya
authors: Shiro
authors: S
authors: Akinaga
authors: Narikazu
authors: N
authors: Boku
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011760:Pyrrolidinones / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011804:Quinolines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C551661:ARQ 197; D047428:Protein Kinase Inhibitors; D011760:Pyrrolidinones; D011804:Quinolines; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met