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Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08
BACKGROUND: Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC). METHODS: This Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who a...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652864/ https://www.ncbi.nlm.nih.gov/pubmed/32863385 http://dx.doi.org/10.1038/s41416-020-01042-w |
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author | Masuishi, Toshiki Tsuji, Akihito Kotaka, Masahito Nakamura, Masato Kochi, Mitsugu Takagane, Akinori Shimada, Ken Denda, Tadamichi Segawa, Yoshihiko Tanioka, Hiroaki Hara, Hiroki Sagawa, Tamotsu Watanabe, Takanori Takahashi, Takao Negoro, Yuji Manaka, Dai Fujita, Hideto Suto, Takeshi Takeuchi, Masahiro Ichikawa, Wataru Fujii, Masashi |
author_facet | Masuishi, Toshiki Tsuji, Akihito Kotaka, Masahito Nakamura, Masato Kochi, Mitsugu Takagane, Akinori Shimada, Ken Denda, Tadamichi Segawa, Yoshihiko Tanioka, Hiroaki Hara, Hiroki Sagawa, Tamotsu Watanabe, Takanori Takahashi, Takao Negoro, Yuji Manaka, Dai Fujita, Hideto Suto, Takeshi Takeuchi, Masahiro Ichikawa, Wataru Fujii, Masashi |
author_sort | Masuishi, Toshiki |
collection | PubMed |
description | BACKGROUND: Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC). METHODS: This Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who achieved clinical benefit with first-line cetuximab-containing therapy. The primary endpoint was 3-month progression-free survival (PFS) rate. A sample size was calculated; 30 patients with a 3-month PFS rate of 45% deemed promising and 15% unacceptable. Patients with greater and less than the cut-off value of cetuximab-free intervals (CFIs) were classified into the long and short CFI groups, respectively, in subgroup analyses. RESULTS: Among 34 eligible patients who received treatment at least once, 3-month PFS rate was 44.1% (95% confidence interval, 27.4–60.8%). The median PFS and overall survival (OS) were 2.4 and 8.2 months, respectively. The response and disease control rates were 2.9 and 55.9%, respectively. PFS and OS were significantly longer in the long- than in the short CFI group. CONCLUSIONS: Irinotecan plus cetuximab rechallenge as third-line treatment for KRAS wild-type mCRC was safe and had promising activity, especially in those with a long CFI, warranting further investigation in a Phase 3 randomised trial. CLINICAL TRIAL REGISTRATION: UMIN000010638 |
format | Online Article Text |
id | pubmed-7652864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76528642021-08-31 Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08 Masuishi, Toshiki Tsuji, Akihito Kotaka, Masahito Nakamura, Masato Kochi, Mitsugu Takagane, Akinori Shimada, Ken Denda, Tadamichi Segawa, Yoshihiko Tanioka, Hiroaki Hara, Hiroki Sagawa, Tamotsu Watanabe, Takanori Takahashi, Takao Negoro, Yuji Manaka, Dai Fujita, Hideto Suto, Takeshi Takeuchi, Masahiro Ichikawa, Wataru Fujii, Masashi Br J Cancer Article BACKGROUND: Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC). METHODS: This Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who achieved clinical benefit with first-line cetuximab-containing therapy. The primary endpoint was 3-month progression-free survival (PFS) rate. A sample size was calculated; 30 patients with a 3-month PFS rate of 45% deemed promising and 15% unacceptable. Patients with greater and less than the cut-off value of cetuximab-free intervals (CFIs) were classified into the long and short CFI groups, respectively, in subgroup analyses. RESULTS: Among 34 eligible patients who received treatment at least once, 3-month PFS rate was 44.1% (95% confidence interval, 27.4–60.8%). The median PFS and overall survival (OS) were 2.4 and 8.2 months, respectively. The response and disease control rates were 2.9 and 55.9%, respectively. PFS and OS were significantly longer in the long- than in the short CFI group. CONCLUSIONS: Irinotecan plus cetuximab rechallenge as third-line treatment for KRAS wild-type mCRC was safe and had promising activity, especially in those with a long CFI, warranting further investigation in a Phase 3 randomised trial. CLINICAL TRIAL REGISTRATION: UMIN000010638 Nature Publishing Group UK 2020-08-31 2020-11-10 /pmc/articles/PMC7652864/ /pubmed/32863385 http://dx.doi.org/10.1038/s41416-020-01042-w Text en © The Author(s), under exclusive licence to Cancer Research UK 2020 https://creativecommons.org/licenses/by/4.0/Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0). |
spellingShingle | Article Masuishi, Toshiki Tsuji, Akihito Kotaka, Masahito Nakamura, Masato Kochi, Mitsugu Takagane, Akinori Shimada, Ken Denda, Tadamichi Segawa, Yoshihiko Tanioka, Hiroaki Hara, Hiroki Sagawa, Tamotsu Watanabe, Takanori Takahashi, Takao Negoro, Yuji Manaka, Dai Fujita, Hideto Suto, Takeshi Takeuchi, Masahiro Ichikawa, Wataru Fujii, Masashi Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08 |
title | Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08 |
title_full | Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08 |
title_fullStr | Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08 |
title_full_unstemmed | Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08 |
title_short | Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08 |
title_sort | phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in kras wild-type metastatic colorectal cancer: jaccro cc-08 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652864/ https://www.ncbi.nlm.nih.gov/pubmed/32863385 http://dx.doi.org/10.1038/s41416-020-01042-w |
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