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The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma

Immunotherapy-based monotherapy treatment in metastatic pancreatic ductal adenocarcinoma (mPDAC) has shown limited benefit outside of the mismatch repair deficiency setting, while safety and efficacy of combining dual-checkpoint inhibitor immunotherapy with chemotherapy remains uncertain. Here, we p...

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Autores principales: Renouf, Daniel J., Loree, Jonathan M., Knox, Jennifer J., Topham, James T., Kavan, Petr, Jonker, Derek, Welch, Stephen, Couture, Felix, Lemay, Frederic, Tehfe, Mustapha, Harb, Mohammed, Aucoin, Nathalie, Ko, Yoo-Joung, Tang, Patricia A., Ramjeesingh, Ravi, Meyers, Brandon M., Kim, Christina A., Du, Pan, Jia, Shidong, Schaeffer, David F., Gill, Sharlene, Tu, Dongsheng, O’Callaghan, Chris J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9418247/
https://www.ncbi.nlm.nih.gov/pubmed/36028483
http://dx.doi.org/10.1038/s41467-022-32591-8
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author Renouf, Daniel J.
Loree, Jonathan M.
Knox, Jennifer J.
Topham, James T.
Kavan, Petr
Jonker, Derek
Welch, Stephen
Couture, Felix
Lemay, Frederic
Tehfe, Mustapha
Harb, Mohammed
Aucoin, Nathalie
Ko, Yoo-Joung
Tang, Patricia A.
Ramjeesingh, Ravi
Meyers, Brandon M.
Kim, Christina A.
Du, Pan
Jia, Shidong
Schaeffer, David F.
Gill, Sharlene
Tu, Dongsheng
O’Callaghan, Chris J
author_facet Renouf, Daniel J.
Loree, Jonathan M.
Knox, Jennifer J.
Topham, James T.
Kavan, Petr
Jonker, Derek
Welch, Stephen
Couture, Felix
Lemay, Frederic
Tehfe, Mustapha
Harb, Mohammed
Aucoin, Nathalie
Ko, Yoo-Joung
Tang, Patricia A.
Ramjeesingh, Ravi
Meyers, Brandon M.
Kim, Christina A.
Du, Pan
Jia, Shidong
Schaeffer, David F.
Gill, Sharlene
Tu, Dongsheng
O’Callaghan, Chris J
author_sort Renouf, Daniel J.
collection PubMed
description Immunotherapy-based monotherapy treatment in metastatic pancreatic ductal adenocarcinoma (mPDAC) has shown limited benefit outside of the mismatch repair deficiency setting, while safety and efficacy of combining dual-checkpoint inhibitor immunotherapy with chemotherapy remains uncertain. Here, we present results from the CCTG PA.7 study (NCT02879318), a randomized phase II trial comparing gemcitabine and nab-paclitaxel with and without immune checkpoint inhibitors durvalumab and tremelimumab in 180 patients with mPDAC. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and objective response rate. Results of the trial were negative as combination immunotherapy did not improve survival among the unselected patient population (p = 0.72) and toxicity was limited to elevation of lymphocytes in the combination immunotherapy group (p = 0.02). Exploratory baseline circulating tumor DNA (ctDNA) sequencing revealed increased survival for patients with KRAS wildtype tumors in both the combination immunotherapy (p = 0.001) and chemotherapy (p = 0.004) groups. These data support the utility of ctDNA analysis in PDAC and the prognostic value of ctDNA-based KRAS mutation status.
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spelling pubmed-94182472022-08-28 The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma Renouf, Daniel J. Loree, Jonathan M. Knox, Jennifer J. Topham, James T. Kavan, Petr Jonker, Derek Welch, Stephen Couture, Felix Lemay, Frederic Tehfe, Mustapha Harb, Mohammed Aucoin, Nathalie Ko, Yoo-Joung Tang, Patricia A. Ramjeesingh, Ravi Meyers, Brandon M. Kim, Christina A. Du, Pan Jia, Shidong Schaeffer, David F. Gill, Sharlene Tu, Dongsheng O’Callaghan, Chris J Nat Commun Article Immunotherapy-based monotherapy treatment in metastatic pancreatic ductal adenocarcinoma (mPDAC) has shown limited benefit outside of the mismatch repair deficiency setting, while safety and efficacy of combining dual-checkpoint inhibitor immunotherapy with chemotherapy remains uncertain. Here, we present results from the CCTG PA.7 study (NCT02879318), a randomized phase II trial comparing gemcitabine and nab-paclitaxel with and without immune checkpoint inhibitors durvalumab and tremelimumab in 180 patients with mPDAC. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and objective response rate. Results of the trial were negative as combination immunotherapy did not improve survival among the unselected patient population (p = 0.72) and toxicity was limited to elevation of lymphocytes in the combination immunotherapy group (p = 0.02). Exploratory baseline circulating tumor DNA (ctDNA) sequencing revealed increased survival for patients with KRAS wildtype tumors in both the combination immunotherapy (p = 0.001) and chemotherapy (p = 0.004) groups. These data support the utility of ctDNA analysis in PDAC and the prognostic value of ctDNA-based KRAS mutation status. Nature Publishing Group UK 2022-08-26 /pmc/articles/PMC9418247/ /pubmed/36028483 http://dx.doi.org/10.1038/s41467-022-32591-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Renouf, Daniel J.
Loree, Jonathan M.
Knox, Jennifer J.
Topham, James T.
Kavan, Petr
Jonker, Derek
Welch, Stephen
Couture, Felix
Lemay, Frederic
Tehfe, Mustapha
Harb, Mohammed
Aucoin, Nathalie
Ko, Yoo-Joung
Tang, Patricia A.
Ramjeesingh, Ravi
Meyers, Brandon M.
Kim, Christina A.
Du, Pan
Jia, Shidong
Schaeffer, David F.
Gill, Sharlene
Tu, Dongsheng
O’Callaghan, Chris J
The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma
title The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma
title_full The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma
title_fullStr The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma
title_full_unstemmed The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma
title_short The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma
title_sort cctg pa.7 phase ii trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9418247/
https://www.ncbi.nlm.nih.gov/pubmed/36028483
http://dx.doi.org/10.1038/s41467-022-32591-8
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