Evidence map›Paper›PMID 26123926›Full record

Trial reportInvestigational new drugs2015

Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer.

Sara M Tolaney, Sally Tan, Hao Guo, William Barry, Eliezer Van Allen, Nikhil Wagle, Jane Brock, Katherine Larrabee, Cloud Paweletz, Elena Ivanova and 6 more

Abstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  18. Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) Signaling.Medical science monitor : international medical journal of experimental and clinical research · 2019
    Article
  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Sara M TolaneyDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA. stolaney@partners.org.
Sally TanHarvard Medical School, Boston, MA, USA.
Hao GuoDepartment of Biostatistics and Computation Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
William BarryDepartment of Biostatistics and Computation Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Eliezer Van AllenCancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nikhil WagleDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
Jane BrockDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Katherine LarrabeeDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
Cloud PaweletzDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
Elena IvanovaDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
Pasi JanneDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
Beth OvermoyerDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
John J WrightCancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA.
Geoffrey I ShapiroDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
Eric P WinerDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.
Ian E KropDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Yawkey 1257, Boston, MA, 02215, USA.

Funding

Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
NCI NIH HHS T32 CA009172
6 · The paper itself

Abstract

backgroundMET 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.

methodsPatients 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.

results22 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).

conclusionThis 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.

Indexed as

AdultAgedAntineoplastic AgentsBiomarkers, TumorDisease-Free SurvivalDose-Response Relationship, DrugFemaleHumansMiddle AgedNeoplasm MetastasisProto-Oncogene Proteins c-metPyrrolidinonesQuinolinesTriple Negative Breast NeoplasmsAntineoplastic AgentsARQ 197Biomarkers, TumorProto-Oncogene Proteins c-metPyrrolidinonesQuinolinesARQ 197METTivantinibTriple-negative breast cancer

Identifiers

PMID26123926
PMCPMC4608248

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.