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Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report

ROS1 tyrosine kinase inhibitors (TKIs) were found to provide a substantial clinical benefit for patients with advanced ROS1-positive (ROS1+) NSCLC. Nevertheless, TKI resistance inevitably develops with different mechanisms, preventing prolonged responses. For this reason, next-generation compounds a...

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Autores principales: Pizzutilo, Elio Gregory, Agostara, Alberto Giuseppe, Roazzi, Laura, Romanò, Rebecca, Motta, Valentina, Lauricella, Calogero, Marrapese, Giovanna, Cerea, Giulio, Signorelli, Diego, Veronese, Silvio Marco, Giannetta, Laura Giuseppina, Sartore-Bianchi, Andrea, Siena, Salvatore
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10689265/
https://www.ncbi.nlm.nih.gov/pubmed/38047274
http://dx.doi.org/10.1016/j.jtocrr.2023.100555
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author Pizzutilo, Elio Gregory
Agostara, Alberto Giuseppe
Roazzi, Laura
Romanò, Rebecca
Motta, Valentina
Lauricella, Calogero
Marrapese, Giovanna
Cerea, Giulio
Signorelli, Diego
Veronese, Silvio Marco
Giannetta, Laura Giuseppina
Sartore-Bianchi, Andrea
Siena, Salvatore
author_facet Pizzutilo, Elio Gregory
Agostara, Alberto Giuseppe
Roazzi, Laura
Romanò, Rebecca
Motta, Valentina
Lauricella, Calogero
Marrapese, Giovanna
Cerea, Giulio
Signorelli, Diego
Veronese, Silvio Marco
Giannetta, Laura Giuseppina
Sartore-Bianchi, Andrea
Siena, Salvatore
author_sort Pizzutilo, Elio Gregory
collection PubMed
description ROS1 tyrosine kinase inhibitors (TKIs) were found to provide a substantial clinical benefit for patients with advanced ROS1-positive (ROS1+) NSCLC. Nevertheless, TKI resistance inevitably develops with different mechanisms, preventing prolonged responses. For this reason, next-generation compounds are under clinical development. ROS1 F2004 substitutions have been previously detected on circulating tumor DNA of patients progressing to entrectinib. Hereby, we report the case of a patient with ROS1+ NSCLC in which F2004V-acquired mutation was detected on a site of disease progression, after entrectinib and crizotinib failure. A subsequent treatment with next-generation TKI repotrectinib led to disease response, providing the first clinical evidence of activity of repotrectinib against F2004V resistance mutation.
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spelling pubmed-106892652023-12-02 Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report Pizzutilo, Elio Gregory Agostara, Alberto Giuseppe Roazzi, Laura Romanò, Rebecca Motta, Valentina Lauricella, Calogero Marrapese, Giovanna Cerea, Giulio Signorelli, Diego Veronese, Silvio Marco Giannetta, Laura Giuseppina Sartore-Bianchi, Andrea Siena, Salvatore JTO Clin Res Rep Case Report ROS1 tyrosine kinase inhibitors (TKIs) were found to provide a substantial clinical benefit for patients with advanced ROS1-positive (ROS1+) NSCLC. Nevertheless, TKI resistance inevitably develops with different mechanisms, preventing prolonged responses. For this reason, next-generation compounds are under clinical development. ROS1 F2004 substitutions have been previously detected on circulating tumor DNA of patients progressing to entrectinib. Hereby, we report the case of a patient with ROS1+ NSCLC in which F2004V-acquired mutation was detected on a site of disease progression, after entrectinib and crizotinib failure. A subsequent treatment with next-generation TKI repotrectinib led to disease response, providing the first clinical evidence of activity of repotrectinib against F2004V resistance mutation. Elsevier 2023-07-26 /pmc/articles/PMC10689265/ /pubmed/38047274 http://dx.doi.org/10.1016/j.jtocrr.2023.100555 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Case Report
Pizzutilo, Elio Gregory
Agostara, Alberto Giuseppe
Roazzi, Laura
Romanò, Rebecca
Motta, Valentina
Lauricella, Calogero
Marrapese, Giovanna
Cerea, Giulio
Signorelli, Diego
Veronese, Silvio Marco
Giannetta, Laura Giuseppina
Sartore-Bianchi, Andrea
Siena, Salvatore
Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report
title Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report
title_full Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report
title_fullStr Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report
title_full_unstemmed Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report
title_short Repotrectinib Overcomes F2004V Resistance Mutation in ROS1-Rearranged NSCLC: A Case Report
title_sort repotrectinib overcomes f2004v resistance mutation in ros1-rearranged nsclc: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10689265/
https://www.ncbi.nlm.nih.gov/pubmed/38047274
http://dx.doi.org/10.1016/j.jtocrr.2023.100555
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