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Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer
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 independe...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608248/ https://www.ncbi.nlm.nih.gov/pubmed/26123926 http://dx.doi.org/10.1007/s10637-015-0269-8 |
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author | Tolaney, Sara M. Tan, Sally Guo, Hao Barry, William Van Allen, Eliezer Wagle, Nikhil Brock, Jane Larrabee, Katherine Paweletz, Cloud Ivanova, Elena Janne, Pasi Overmoyer, Beth Wright, John J. Shapiro, Geoffrey I. Winer, Eric P. Krop, Ian E. |
author_facet | Tolaney, Sara M. Tan, Sally Guo, Hao Barry, William Van Allen, Eliezer Wagle, Nikhil Brock, Jane Larrabee, Katherine Paweletz, Cloud Ivanova, Elena Janne, Pasi Overmoyer, Beth Wright, John J. Shapiro, Geoffrey I. Winer, Eric P. Krop, Ian E. |
author_sort | Tolaney, Sara M. |
collection | PubMed |
description | 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). Conclusion 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. |
format | Online Article Text |
id | pubmed-4608248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-46082482016-03-29 Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer Tolaney, Sara M. Tan, Sally Guo, Hao Barry, William Van Allen, Eliezer Wagle, Nikhil Brock, Jane Larrabee, Katherine Paweletz, Cloud Ivanova, Elena Janne, Pasi Overmoyer, Beth Wright, John J. Shapiro, Geoffrey I. Winer, Eric P. Krop, Ian E. Invest New Drugs Phase II Studies 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). Conclusion 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. Springer US 2015-07-01 2015 /pmc/articles/PMC4608248/ /pubmed/26123926 http://dx.doi.org/10.1007/s10637-015-0269-8 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Phase II Studies Tolaney, Sara M. Tan, Sally Guo, Hao Barry, William Van Allen, Eliezer Wagle, Nikhil Brock, Jane Larrabee, Katherine Paweletz, Cloud Ivanova, Elena Janne, Pasi Overmoyer, Beth Wright, John J. Shapiro, Geoffrey I. Winer, Eric P. Krop, Ian E. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer |
title | Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer |
title_full | Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer |
title_fullStr | Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer |
title_full_unstemmed | Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer |
title_short | Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer |
title_sort | phase ii study of tivantinib (arq 197) in patients with metastatic triple-negative breast cancer |
topic | Phase II Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608248/ https://www.ncbi.nlm.nih.gov/pubmed/26123926 http://dx.doi.org/10.1007/s10637-015-0269-8 |
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