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Long‐term effects of crizotinib in ALK‐positive tumors (excluding NSCLC): A phase 1b open‐label study

Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK‐positive or ROS1‐positive advanced non‐small‐cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large‐cell ly...

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Autores principales: Gambacorti‐Passerini, Carlo, Orlov, Sergey, Zhang, Li, Braiteh, Fadi, Huang, Huiqiang, Esaki, Taito, Horibe, Keizo, Ahn, Jin‐Seok, Beck, Joseph T., Edenfield, William Jeffrey, Shi, Yuankai, Taylor, Matthew, Tamura, Kenji, Van Tine, Brian A., Wu, Shang‐Ju, Paolini, Jolanda, Selaru, Paulina, Kim, Tae Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947833/
https://www.ncbi.nlm.nih.gov/pubmed/29352732
http://dx.doi.org/10.1002/ajh.25043
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author Gambacorti‐Passerini, Carlo
Orlov, Sergey
Zhang, Li
Braiteh, Fadi
Huang, Huiqiang
Esaki, Taito
Horibe, Keizo
Ahn, Jin‐Seok
Beck, Joseph T.
Edenfield, William Jeffrey
Shi, Yuankai
Taylor, Matthew
Tamura, Kenji
Van Tine, Brian A.
Wu, Shang‐Ju
Paolini, Jolanda
Selaru, Paulina
Kim, Tae Min
author_facet Gambacorti‐Passerini, Carlo
Orlov, Sergey
Zhang, Li
Braiteh, Fadi
Huang, Huiqiang
Esaki, Taito
Horibe, Keizo
Ahn, Jin‐Seok
Beck, Joseph T.
Edenfield, William Jeffrey
Shi, Yuankai
Taylor, Matthew
Tamura, Kenji
Van Tine, Brian A.
Wu, Shang‐Ju
Paolini, Jolanda
Selaru, Paulina
Kim, Tae Min
author_sort Gambacorti‐Passerini, Carlo
collection PubMed
description Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK‐positive or ROS1‐positive advanced non‐small‐cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large‐cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single‐arm, open‐label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK‐positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily. Primary endpoints were safety and objective responses based on Response Evaluation Criteria in Solid Tumors version 1.1 or National Cancer Institute International Response Criteria. Forty‐four patients were enrolled (lymphoma, n = 18; IMT, n = 9; other tumors, n = 17). The objective response rate was 53% (95% confidence interval [CI], 28–77) for lymphoma, with 8 complete responses (CRs) and 1 partial response (PR); 67% (95% CI, 30–93) for IMTs, with 1 CR and 5 PRs; and 12% (95% CI, 2–36) for other tumors, with 2 PRs in patients affected by colon carcinoma and medullary thyroid cancer, respectively. The median duration of treatment was almost 3 years for patients with lymphoma and IMTs, with 2‐year progression‐free survival of 63% and 67%, respectively. The most common treatment‐related adverse events were diarrhea (45.5%) and vision disorders (45.5%), mostly grade 1. These findings indicate strong and durable activity of crizotinib in ALK‐positive lymphomas and IMTs. The safety profile was consistent with the known safety profile of crizotinib even with long‐term treatment.
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spelling pubmed-59478332018-05-17 Long‐term effects of crizotinib in ALK‐positive tumors (excluding NSCLC): A phase 1b open‐label study Gambacorti‐Passerini, Carlo Orlov, Sergey Zhang, Li Braiteh, Fadi Huang, Huiqiang Esaki, Taito Horibe, Keizo Ahn, Jin‐Seok Beck, Joseph T. Edenfield, William Jeffrey Shi, Yuankai Taylor, Matthew Tamura, Kenji Van Tine, Brian A. Wu, Shang‐Ju Paolini, Jolanda Selaru, Paulina Kim, Tae Min Am J Hematol Research Articles Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK‐positive or ROS1‐positive advanced non‐small‐cell lung cancer (NSCLC). However, ALK rearrangements are also implicated in other malignancies, including anaplastic large‐cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single‐arm, open‐label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK‐positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily. Primary endpoints were safety and objective responses based on Response Evaluation Criteria in Solid Tumors version 1.1 or National Cancer Institute International Response Criteria. Forty‐four patients were enrolled (lymphoma, n = 18; IMT, n = 9; other tumors, n = 17). The objective response rate was 53% (95% confidence interval [CI], 28–77) for lymphoma, with 8 complete responses (CRs) and 1 partial response (PR); 67% (95% CI, 30–93) for IMTs, with 1 CR and 5 PRs; and 12% (95% CI, 2–36) for other tumors, with 2 PRs in patients affected by colon carcinoma and medullary thyroid cancer, respectively. The median duration of treatment was almost 3 years for patients with lymphoma and IMTs, with 2‐year progression‐free survival of 63% and 67%, respectively. The most common treatment‐related adverse events were diarrhea (45.5%) and vision disorders (45.5%), mostly grade 1. These findings indicate strong and durable activity of crizotinib in ALK‐positive lymphomas and IMTs. The safety profile was consistent with the known safety profile of crizotinib even with long‐term treatment. John Wiley and Sons Inc. 2018-02-08 2018-05 /pmc/articles/PMC5947833/ /pubmed/29352732 http://dx.doi.org/10.1002/ajh.25043 Text en © 2018 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Gambacorti‐Passerini, Carlo
Orlov, Sergey
Zhang, Li
Braiteh, Fadi
Huang, Huiqiang
Esaki, Taito
Horibe, Keizo
Ahn, Jin‐Seok
Beck, Joseph T.
Edenfield, William Jeffrey
Shi, Yuankai
Taylor, Matthew
Tamura, Kenji
Van Tine, Brian A.
Wu, Shang‐Ju
Paolini, Jolanda
Selaru, Paulina
Kim, Tae Min
Long‐term effects of crizotinib in ALK‐positive tumors (excluding NSCLC): A phase 1b open‐label study
title Long‐term effects of crizotinib in ALK‐positive tumors (excluding NSCLC): A phase 1b open‐label study
title_full Long‐term effects of crizotinib in ALK‐positive tumors (excluding NSCLC): A phase 1b open‐label study
title_fullStr Long‐term effects of crizotinib in ALK‐positive tumors (excluding NSCLC): A phase 1b open‐label study
title_full_unstemmed Long‐term effects of crizotinib in ALK‐positive tumors (excluding NSCLC): A phase 1b open‐label study
title_short Long‐term effects of crizotinib in ALK‐positive tumors (excluding NSCLC): A phase 1b open‐label study
title_sort long‐term effects of crizotinib in alk‐positive tumors (excluding nsclc): a phase 1b open‐label study
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947833/
https://www.ncbi.nlm.nih.gov/pubmed/29352732
http://dx.doi.org/10.1002/ajh.25043
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