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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
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.
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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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