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Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study

BACKGROUND: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. METHODS: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n =...

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Autores principales: Orlov, Sergey V., Iyevleva, Aglaya G., Filippova, Elena A., Lozhkina, Alexandra M., Odintsova, Svetlana V., Sokolova, Tatiana N., Mitiushkina, Natalia V., Tiurin, Vladislav I., Preobrazhenskaya, Elena V., Romanko, Alexandr A., Martianov, Alexandr S., Ivantsov, Alexandr O., Aleksakhina, Svetlana N., Togo, Alexandr V., Imyanitov, Evgeny N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144735/
https://www.ncbi.nlm.nih.gov/pubmed/34030112
http://dx.doi.org/10.1016/j.tranon.2021.101121
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author Orlov, Sergey V.
Iyevleva, Aglaya G.
Filippova, Elena A.
Lozhkina, Alexandra M.
Odintsova, Svetlana V.
Sokolova, Tatiana N.
Mitiushkina, Natalia V.
Tiurin, Vladislav I.
Preobrazhenskaya, Elena V.
Romanko, Alexandr A.
Martianov, Alexandr S.
Ivantsov, Alexandr O.
Aleksakhina, Svetlana N.
Togo, Alexandr V.
Imyanitov, Evgeny N.
author_facet Orlov, Sergey V.
Iyevleva, Aglaya G.
Filippova, Elena A.
Lozhkina, Alexandra M.
Odintsova, Svetlana V.
Sokolova, Tatiana N.
Mitiushkina, Natalia V.
Tiurin, Vladislav I.
Preobrazhenskaya, Elena V.
Romanko, Alexandr A.
Martianov, Alexandr S.
Ivantsov, Alexandr O.
Aleksakhina, Svetlana N.
Togo, Alexandr V.
Imyanitov, Evgeny N.
author_sort Orlov, Sergey V.
collection PubMed
description BACKGROUND: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. METHODS: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program. RESULTS: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared to the remaining patients (1.1 months vs. 23.7 months and 10.5 months vs. not reached, respectively; p < 0.0001 for both comparisons). ALK translocation variants were known for 28 patients; there was no statistical difference between patients with V.1 and V.3 rearrangements with regard to the OS or PFS. CONCLUSION: Use of lorlatinib results in excellent disease outcomes, however caution must be taken for patients experiencing no adverse effects from this drug.
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spelling pubmed-81447352021-06-04 Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study Orlov, Sergey V. Iyevleva, Aglaya G. Filippova, Elena A. Lozhkina, Alexandra M. Odintsova, Svetlana V. Sokolova, Tatiana N. Mitiushkina, Natalia V. Tiurin, Vladislav I. Preobrazhenskaya, Elena V. Romanko, Alexandr A. Martianov, Alexandr S. Ivantsov, Alexandr O. Aleksakhina, Svetlana N. Togo, Alexandr V. Imyanitov, Evgeny N. Transl Oncol Original Research BACKGROUND: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. METHODS: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program. RESULTS: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared to the remaining patients (1.1 months vs. 23.7 months and 10.5 months vs. not reached, respectively; p < 0.0001 for both comparisons). ALK translocation variants were known for 28 patients; there was no statistical difference between patients with V.1 and V.3 rearrangements with regard to the OS or PFS. CONCLUSION: Use of lorlatinib results in excellent disease outcomes, however caution must be taken for patients experiencing no adverse effects from this drug. Neoplasia Press 2021-05-21 /pmc/articles/PMC8144735/ /pubmed/34030112 http://dx.doi.org/10.1016/j.tranon.2021.101121 Text en © 2021 The Authors. Published by Elsevier Inc. 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 Research
Orlov, Sergey V.
Iyevleva, Aglaya G.
Filippova, Elena A.
Lozhkina, Alexandra M.
Odintsova, Svetlana V.
Sokolova, Tatiana N.
Mitiushkina, Natalia V.
Tiurin, Vladislav I.
Preobrazhenskaya, Elena V.
Romanko, Alexandr A.
Martianov, Alexandr S.
Ivantsov, Alexandr O.
Aleksakhina, Svetlana N.
Togo, Alexandr V.
Imyanitov, Evgeny N.
Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study
title Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study
title_full Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study
title_fullStr Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study
title_full_unstemmed Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study
title_short Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study
title_sort efficacy of lorlatinib in lung carcinomas carrying distinct alk translocation variants: the results of a single-center study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144735/
https://www.ncbi.nlm.nih.gov/pubmed/34030112
http://dx.doi.org/10.1016/j.tranon.2021.101121
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