title: Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer.
abstract: BACKGROUND
  MET expression and activation appear to be important for initiation and progression of triple-negative breast cancer. Tivantinib (ARQ 197) is an orally administered agent that targets MET, although recent preclinical data suggests the agent may have mechanisms of action that are independent of MET signaling. We conducted a phase 2 study of tivantinib monotherapy in patients with metastatic triple-negative breast cancer.
  
  
  METHODS
  Patients with metastatic triple-negative breast cancer who had received 1 to 3 prior lines of chemotherapy in the metastatic setting were enrolled into this two-stage, single arm phase 2 study. Treatment consisted of twice daily oral dosing of tivantinib (360 mg po bid) during a 21-day cycle. Patients underwent restaging scans at 6 weeks, and then every 9 weeks. Tumor biomarkers that might predict response to tivantinib were explored.
  
  
  RESULTS
  22 patients were enrolled. The overall response rate was 5 % (95 % CI 0-25 %) and the 6-month progression-free survival (PFS) was 5 % (95 % CI 0-25 %), with one patient achieving a partial response (PR). Toxicity was minimal with only 5 grade ≥3 adverse events (one grade 3 anemia, one grade 3 fatigue, and 3 patients with grade 3/4 neutropenia).
  
  
  CONCLUSIONS
  This study represents the first evaluation of tivantinib for the treatment of metastatic triple-negative breast cancer. These results suggest that single agent tivantinib is well tolerated, but did not meet prespecified statistical targets for efficacy.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA. stolaney@partners.org.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Tolaney
authors.affiliation: Harvard Medical School, Boston, MA, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Biostatistics and Computation Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Biostatistics and Computation Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Barry
authors.affiliation: Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Van Allen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.|Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Wagle
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Brock
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Larrabee
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.|Belfer Institute for Applied Cancer Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Cloud
authors.initials: C
authors.lastname: Paweletz
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.|Belfer Institute for Applied Cancer Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Ivanova
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.|Belfer Institute for Applied Cancer Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Pasi
authors.initials: P
authors.lastname: Janne
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Overmoyer
authors.affiliation: Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: Shapiro
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
authors.forename: Ian E
authors.initials: IE
authors.lastname: Krop
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: C551661:ARQ 197; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011760:Pyrrolidinones; D011804:Quinolines; D019859:Proto-Oncogene Proteins c-met
keywords: ARQ 197; MET; Tivantinib; Triple-negative breast cancer