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Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials

Panitumumab is approved for RAS wild‐type metastatic colorectal cancer and was evaluated in Phase III (PRIME, NCT00364013) and Phase II (PEAK, NCT00819780) first‐line randomised studies. This retrospective analysis of these trials investigated efficacy and toxicity of panitumumab‐based maintenance a...

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Autores principales: Modest, Dominik Paul, Rivera, Fernando, Bachet, Jean‐Baptiste, de Braud, Filippo, Pietrantonio, Filippo, Koukakis, Reija, Demonty, Gaston, Douillard, Jean‐Yves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590196/
https://www.ncbi.nlm.nih.gov/pubmed/30614531
http://dx.doi.org/10.1002/ijc.32110
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author Modest, Dominik Paul
Rivera, Fernando
Bachet, Jean‐Baptiste
de Braud, Filippo
Pietrantonio, Filippo
Koukakis, Reija
Demonty, Gaston
Douillard, Jean‐Yves
author_facet Modest, Dominik Paul
Rivera, Fernando
Bachet, Jean‐Baptiste
de Braud, Filippo
Pietrantonio, Filippo
Koukakis, Reija
Demonty, Gaston
Douillard, Jean‐Yves
author_sort Modest, Dominik Paul
collection PubMed
description Panitumumab is approved for RAS wild‐type metastatic colorectal cancer and was evaluated in Phase III (PRIME, NCT00364013) and Phase II (PEAK, NCT00819780) first‐line randomised studies. This retrospective analysis of these trials investigated efficacy and toxicity of panitumumab‐based maintenance after oxaliplatin discontinuation in RAS wild‐type patients. First‐line regimens were FOLFOX4 ± panitumumab in PRIME and mFOLFOX6 plus panitumumab or mFOLFOX6 plus bevacizumab in PEAK. Outcomes included median progression‐free survival (PFS) and overall survival (OS), from randomisation and oxaliplatin discontinuation, and toxicity. Overall, median duration of panitumumab plus 5‐fluorouracil/leucovorin (5‐FU/LV) maintenance was 21 (interquartile range: 11–41) weeks; that of 5‐FU/LV ± bevacizumab maintenance was 16 (6–31) weeks. Median OS from randomisation was 40.2 (95% confidence interval: 30.3–50.4) and 39.1 (34.2–63.0) months for panitumumab plus 5‐FU/LV maintenance and 24.1 (17.7–33.0) and 28.9 (21.0–32.0) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. Median PFS from randomisation was 16.6 (11.3–23.6) and 15.4 (11.6–18.4) months for panitumumab plus 5‐FU/LV maintenance and 12.6 (9.4–16.2) and 13.1 (9.5–16.6) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. From oxaliplatin discontinuation, median OS was 33.9 (24.7–42.8) and 33.5 (24.5–54.9) months for panitumumab plus 5‐FU/LV maintenance and 16.4 (12.4–24.1) and 23.3 (15.7–26.3) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively; PFS was 11.7 (7.8–19.2) and 9.7 (5.8–14.8) months and 7.1 (5.6–10.2) and 7.0 (3.9–10.6) months, respectively. The most frequently reported adverse events were rash, fatigue and diarrhoea. Maintenance of panitumumab plus 5‐FU/LV after oxaliplatin discontinuation was well tolerated and may be an acceptable treatment paradigm for patients demonstrating a good response to first‐line treatment. Prospective studies are warranted.
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spelling pubmed-65901962019-07-08 Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials Modest, Dominik Paul Rivera, Fernando Bachet, Jean‐Baptiste de Braud, Filippo Pietrantonio, Filippo Koukakis, Reija Demonty, Gaston Douillard, Jean‐Yves Int J Cancer Cancer Therapy and Prevention Panitumumab is approved for RAS wild‐type metastatic colorectal cancer and was evaluated in Phase III (PRIME, NCT00364013) and Phase II (PEAK, NCT00819780) first‐line randomised studies. This retrospective analysis of these trials investigated efficacy and toxicity of panitumumab‐based maintenance after oxaliplatin discontinuation in RAS wild‐type patients. First‐line regimens were FOLFOX4 ± panitumumab in PRIME and mFOLFOX6 plus panitumumab or mFOLFOX6 plus bevacizumab in PEAK. Outcomes included median progression‐free survival (PFS) and overall survival (OS), from randomisation and oxaliplatin discontinuation, and toxicity. Overall, median duration of panitumumab plus 5‐fluorouracil/leucovorin (5‐FU/LV) maintenance was 21 (interquartile range: 11–41) weeks; that of 5‐FU/LV ± bevacizumab maintenance was 16 (6–31) weeks. Median OS from randomisation was 40.2 (95% confidence interval: 30.3–50.4) and 39.1 (34.2–63.0) months for panitumumab plus 5‐FU/LV maintenance and 24.1 (17.7–33.0) and 28.9 (21.0–32.0) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. Median PFS from randomisation was 16.6 (11.3–23.6) and 15.4 (11.6–18.4) months for panitumumab plus 5‐FU/LV maintenance and 12.6 (9.4–16.2) and 13.1 (9.5–16.6) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively. From oxaliplatin discontinuation, median OS was 33.9 (24.7–42.8) and 33.5 (24.5–54.9) months for panitumumab plus 5‐FU/LV maintenance and 16.4 (12.4–24.1) and 23.3 (15.7–26.3) months for 5‐FU/LV ± bevacizumab maintenance in PRIME and PEAK, respectively; PFS was 11.7 (7.8–19.2) and 9.7 (5.8–14.8) months and 7.1 (5.6–10.2) and 7.0 (3.9–10.6) months, respectively. The most frequently reported adverse events were rash, fatigue and diarrhoea. Maintenance of panitumumab plus 5‐FU/LV after oxaliplatin discontinuation was well tolerated and may be an acceptable treatment paradigm for patients demonstrating a good response to first‐line treatment. Prospective studies are warranted. John Wiley & Sons, Inc. 2019-01-24 2019-07-15 /pmc/articles/PMC6590196/ /pubmed/30614531 http://dx.doi.org/10.1002/ijc.32110 Text en © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Cancer Therapy and Prevention
Modest, Dominik Paul
Rivera, Fernando
Bachet, Jean‐Baptiste
de Braud, Filippo
Pietrantonio, Filippo
Koukakis, Reija
Demonty, Gaston
Douillard, Jean‐Yves
Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials
title Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials
title_full Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials
title_fullStr Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials
title_full_unstemmed Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials
title_short Panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: A retrospective analysis of two randomised trials
title_sort panitumumab‐based maintenance after oxaliplatin discontinuation in metastatic colorectal cancer: a retrospective analysis of two randomised trials
topic Cancer Therapy and Prevention
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590196/
https://www.ncbi.nlm.nih.gov/pubmed/30614531
http://dx.doi.org/10.1002/ijc.32110
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