title: A phase 2 multicenter study of tivantinib (ARQ 197) monotherapy in patients with relapsed or refractory germ cell tumors.
abstract: BACKGROUND
  Tivantinib is a selective, small-molecule inhibitor of the MET receptor tyrosine kinase. Preclinical and phase 1 data suggested a possible role for MET in the pathophysiology of germ cell tumors (GCTs) and a potential clinical benefit from tivantinib in patients with these tumors.
  
  
  METHODS
  Men (≥ 16 years) with relapsed or refractory, histologically confirmed, non-central nervous system GCTs received oral tivantinib 360 mg twice daily in 28-day cycles until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate in the first 4 cycles, with study termination for <2 responses among the first 21 patients. Secondary endpoints included 12-week progression-free survival (PFS), overall survival (OS), and safety.
  
  
  RESULTS
  Twenty-seven patients were enrolled in 9 months (median age, 32 years). Most patients had tumors with nonseminoma histology (n = 25), and primary tumor sites were testis (n = 24) and mediastinum (n = 3). Among 25 evaluable patients, no objective responses were observed; accrual was halted when the 21st patient became evaluable. Best response was stable disease (n = 5). Median PFS was 1 month, the 12-week PFS rate was 21 %, and median OS was 6 months. Grade 3 or 4 adverse events considered related to study drug included grade 3 pneumonia and grade 3 syncope (n = 1, each).
  
  
  CONCLUSIONS
  Tivantinib was well tolerated but did not demonstrate single-agent activity in patients with relapsed/refractory GCTs. Rapid accrual to this phase 2 trial was achieved in this rare patient population through multicenter collaboration.
authors: Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. feldmand@mskcc.org
authors: Darren R
authors: DR
authors: Feldman
authors: Lawrence H
authors: LH
authors: Einhorn
authors: David I
authors: DI
authors: Quinn
authors: Yohann
authors: Y
authors: Loriot
authors: Johnathan K
authors: JK
authors: Joffe
authors: David J
authors: DJ
authors: Vaughn
authors: Aude
authors: A
authors: Fléchon
authors: Julio
authors: J
authors: Hajdenberg
authors: Abdel-Baset
authors: AB
authors: Halim
authors: Hamim
authors: H
authors: Zahir
authors: Robert J
authors: RJ
authors: Motzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D003710:Demography; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011760:Pyrrolidinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C551661:ARQ 197; D000970:Antineoplastic Agents; D011760:Pyrrolidinones; D011804:Quinolines; D019859:Proto-Oncogene Proteins c-met