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A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma
Purpose: Despite the wide adoption of tumor molecular profiling, there is a dearth of evidence linking molecular biomarkers for treatment selection to prediction of treatment outcomes in patients with metastatic pancreatic cancer. We initiated a pilot study to test the feasibility of designing a lar...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mary Ann Liebert, Inc., publishers
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503449/ https://www.ncbi.nlm.nih.gov/pubmed/31065624 http://dx.doi.org/10.1089/pancan.2019.0003 |
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author | Tesfaye, Anteneh A. Wang, Hongkun Hartley, Marion L. He, Aiwu Ruth Weiner, Louis Gabelia, Nina Kapanadze, Lana Shezad, Muhammad Brody, Jonathan R. Marshall, John L. Pishvaian, Michael J. |
author_facet | Tesfaye, Anteneh A. Wang, Hongkun Hartley, Marion L. He, Aiwu Ruth Weiner, Louis Gabelia, Nina Kapanadze, Lana Shezad, Muhammad Brody, Jonathan R. Marshall, John L. Pishvaian, Michael J. |
author_sort | Tesfaye, Anteneh A. |
collection | PubMed |
description | Purpose: Despite the wide adoption of tumor molecular profiling, there is a dearth of evidence linking molecular biomarkers for treatment selection to prediction of treatment outcomes in patients with metastatic pancreatic cancer. We initiated a pilot study to test the feasibility of designing a larger phase II trial of molecularly tailored treatment for metastatic pancreatic cancer. Methods: Our study aimed to assess the feasibility of following a treatment algorithm based on the expression of three published predictive markers of response to chemotherapy: ribonucleotide reductase catalytic subunit M1 (for gemcitabine); excision repair cross-complementation group 1 (for platinum agents); and thymidylate synthase (for 5-fluorouracil) in patients with untreated, metastatic pancreatic cancer. Results of the tumor biopsy analysis were used to assign patients to one of seven doublet regimens. Key secondary objectives included response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Between December 2012 and March 2015, 30 patients were enrolled into the study. Ten patients failed screening primarily due to inadequate tumor tissue availability. Of the remaining 20 patients, 19 were assigned into 6 different chemotherapy doublets, and achieved an RR of 28%, with a DCR rate of 78%. The median PFS and OS were 5.78 and 8.21 months, respectively. Conclusions: The incorporation of biomarkers into a treatment algorithm is feasible and resulted in a PFS and OS similar to other doublet therapies for patients with metastatic pancreatic cancer. Based on the results from this pilot study, a larger phase II randomized trial of molecularly targeted therapy versus physicians' choice of standard of care has been initiated in the second-line setting (NCT02967770). |
format | Online Article Text |
id | pubmed-6503449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Mary Ann Liebert, Inc., publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-65034492019-05-07 A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma Tesfaye, Anteneh A. Wang, Hongkun Hartley, Marion L. He, Aiwu Ruth Weiner, Louis Gabelia, Nina Kapanadze, Lana Shezad, Muhammad Brody, Jonathan R. Marshall, John L. Pishvaian, Michael J. J Pancreat Cancer Original Article Purpose: Despite the wide adoption of tumor molecular profiling, there is a dearth of evidence linking molecular biomarkers for treatment selection to prediction of treatment outcomes in patients with metastatic pancreatic cancer. We initiated a pilot study to test the feasibility of designing a larger phase II trial of molecularly tailored treatment for metastatic pancreatic cancer. Methods: Our study aimed to assess the feasibility of following a treatment algorithm based on the expression of three published predictive markers of response to chemotherapy: ribonucleotide reductase catalytic subunit M1 (for gemcitabine); excision repair cross-complementation group 1 (for platinum agents); and thymidylate synthase (for 5-fluorouracil) in patients with untreated, metastatic pancreatic cancer. Results of the tumor biopsy analysis were used to assign patients to one of seven doublet regimens. Key secondary objectives included response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Between December 2012 and March 2015, 30 patients were enrolled into the study. Ten patients failed screening primarily due to inadequate tumor tissue availability. Of the remaining 20 patients, 19 were assigned into 6 different chemotherapy doublets, and achieved an RR of 28%, with a DCR rate of 78%. The median PFS and OS were 5.78 and 8.21 months, respectively. Conclusions: The incorporation of biomarkers into a treatment algorithm is feasible and resulted in a PFS and OS similar to other doublet therapies for patients with metastatic pancreatic cancer. Based on the results from this pilot study, a larger phase II randomized trial of molecularly targeted therapy versus physicians' choice of standard of care has been initiated in the second-line setting (NCT02967770). Mary Ann Liebert, Inc., publishers 2019-05-02 /pmc/articles/PMC6503449/ /pubmed/31065624 http://dx.doi.org/10.1089/pancan.2019.0003 Text en © Anteneh A. Tesfaye et al. 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Tesfaye, Anteneh A. Wang, Hongkun Hartley, Marion L. He, Aiwu Ruth Weiner, Louis Gabelia, Nina Kapanadze, Lana Shezad, Muhammad Brody, Jonathan R. Marshall, John L. Pishvaian, Michael J. A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma |
title | A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma |
title_full | A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma |
title_fullStr | A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma |
title_full_unstemmed | A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma |
title_short | A Pilot Trial of Molecularly Tailored Therapy for Patients with Metastatic Pancreatic Ductal Adenocarcinoma |
title_sort | pilot trial of molecularly tailored therapy for patients with metastatic pancreatic ductal adenocarcinoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503449/ https://www.ncbi.nlm.nih.gov/pubmed/31065624 http://dx.doi.org/10.1089/pancan.2019.0003 |
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