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A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib
INTRODUCTION: The central nervous system (CNS) is a common site of progression among patients with ROS1-rearranged lung cancer receiving crizotinib. We conducted a phase 2 study to evaluate the intracranial efficacy of lorlatinib in patients with ROS1-rearranged lung cancer who developed CNS-only pr...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257415/ https://www.ncbi.nlm.nih.gov/pubmed/35815322 http://dx.doi.org/10.1016/j.jtocrr.2022.100347 |
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author | Schneider, Jaime L. Muzikansky, Alona Lin, Jessica J. Krueger, Elizabeth A. Lennes, Inga T. Jacobson, Joseph O. Cheng, Michael Heist, Rebecca S. Piotrowska, Zofia Gainor, Justin F. Shaw, Alice T. Dagogo-Jack, Ibiay |
author_facet | Schneider, Jaime L. Muzikansky, Alona Lin, Jessica J. Krueger, Elizabeth A. Lennes, Inga T. Jacobson, Joseph O. Cheng, Michael Heist, Rebecca S. Piotrowska, Zofia Gainor, Justin F. Shaw, Alice T. Dagogo-Jack, Ibiay |
author_sort | Schneider, Jaime L. |
collection | PubMed |
description | INTRODUCTION: The central nervous system (CNS) is a common site of progression among patients with ROS1-rearranged lung cancer receiving crizotinib. We conducted a phase 2 study to evaluate the intracranial efficacy of lorlatinib in patients with ROS1-rearranged lung cancer who developed CNS-only progression on crizotinib. METHODS: Patients with metastatic ROS1-rearranged lung cancer with CNS-only progression on crizotinib received lorlatinib 100 mg daily. The primary end point was intracranial disease control rate at 12 weeks per modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included intracranial and extracranial progression-free survival, intracranial objective response rate, and safety/tolerability. RESULTS: A total of 16 patients were enrolled between November 2016 and January 2019. Nine patients (56%) had received prior CNS radiation, with a median of 10.9 months between radiation and lorlatinib. At 12 weeks, the intracranial disease control rate was 100% and intracranial objective response rate was 87%. While on study, the complee intracranial response rate was 60%. With median follow-up of 22 months, seven patients experienced disease progression, including five patients with CNS relapse. The median intracranial and extracranial progression-free survivals were 38.8 months (95% confidence interval: 16.9–not reported) and 41.1 months (95% confidence interval: 17.6–not reported), respectively. Molecular analysis of plasma or tissue from patients with extracranial progression on lorlatinib revealed ROS1 G2032R (n = 1), ROS1 L2086F (n = 1), and CCDC6-RET fusion plus ROS1 G2032R (n = 1). The safety profile of lorlatinib was consistent with prior studies. There were 11 patients (69%) who required dose reduction, including one patient who discontinued treatment for grade 3 edema. No grade greater than or equal to 4 adverse events were observed. CONCLUSIONS: Lorlatinib induced durable intracranial responses in patients with ROS1-rearranged NSCLC and prior isolated CNS progression on crizotinib. |
format | Online Article Text |
id | pubmed-9257415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92574152022-07-07 A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib Schneider, Jaime L. Muzikansky, Alona Lin, Jessica J. Krueger, Elizabeth A. Lennes, Inga T. Jacobson, Joseph O. Cheng, Michael Heist, Rebecca S. Piotrowska, Zofia Gainor, Justin F. Shaw, Alice T. Dagogo-Jack, Ibiay JTO Clin Res Rep Original Article INTRODUCTION: The central nervous system (CNS) is a common site of progression among patients with ROS1-rearranged lung cancer receiving crizotinib. We conducted a phase 2 study to evaluate the intracranial efficacy of lorlatinib in patients with ROS1-rearranged lung cancer who developed CNS-only progression on crizotinib. METHODS: Patients with metastatic ROS1-rearranged lung cancer with CNS-only progression on crizotinib received lorlatinib 100 mg daily. The primary end point was intracranial disease control rate at 12 weeks per modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included intracranial and extracranial progression-free survival, intracranial objective response rate, and safety/tolerability. RESULTS: A total of 16 patients were enrolled between November 2016 and January 2019. Nine patients (56%) had received prior CNS radiation, with a median of 10.9 months between radiation and lorlatinib. At 12 weeks, the intracranial disease control rate was 100% and intracranial objective response rate was 87%. While on study, the complee intracranial response rate was 60%. With median follow-up of 22 months, seven patients experienced disease progression, including five patients with CNS relapse. The median intracranial and extracranial progression-free survivals were 38.8 months (95% confidence interval: 16.9–not reported) and 41.1 months (95% confidence interval: 17.6–not reported), respectively. Molecular analysis of plasma or tissue from patients with extracranial progression on lorlatinib revealed ROS1 G2032R (n = 1), ROS1 L2086F (n = 1), and CCDC6-RET fusion plus ROS1 G2032R (n = 1). The safety profile of lorlatinib was consistent with prior studies. There were 11 patients (69%) who required dose reduction, including one patient who discontinued treatment for grade 3 edema. No grade greater than or equal to 4 adverse events were observed. CONCLUSIONS: Lorlatinib induced durable intracranial responses in patients with ROS1-rearranged NSCLC and prior isolated CNS progression on crizotinib. Elsevier 2022-06-08 /pmc/articles/PMC9257415/ /pubmed/35815322 http://dx.doi.org/10.1016/j.jtocrr.2022.100347 Text en © 2022 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 | Original Article Schneider, Jaime L. Muzikansky, Alona Lin, Jessica J. Krueger, Elizabeth A. Lennes, Inga T. Jacobson, Joseph O. Cheng, Michael Heist, Rebecca S. Piotrowska, Zofia Gainor, Justin F. Shaw, Alice T. Dagogo-Jack, Ibiay A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib |
title | A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib |
title_full | A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib |
title_fullStr | A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib |
title_full_unstemmed | A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib |
title_short | A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib |
title_sort | phase 2 study of lorlatinib in patients with ros1-rearranged lung cancer with brain-only progression on crizotinib |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257415/ https://www.ncbi.nlm.nih.gov/pubmed/35815322 http://dx.doi.org/10.1016/j.jtocrr.2022.100347 |
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