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Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis

Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N =...

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Autores principales: Reiter, Andreas, Gotlib, Jason, Álvarez-Twose, Iván, Radia, Deepti H., Lübke, Johannes, Bobbili, Priyanka J., Wang, Aolin, Norregaard, Chelsea, Dimitrijevic, Saša, Sullivan, Erin, Louie-Gao, Melinda, Schwaab, Juliana, Galinsky, Ilene A., Perkins, Cecelia, Sperr, Wolfgang R., Sriskandarajah, Priya, Chin, Andi, Sendhil, Selvam R., Duh, Mei Sheng, Valent, Peter, DeAngelo, Daniel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343245/
https://www.ncbi.nlm.nih.gov/pubmed/35790816
http://dx.doi.org/10.1038/s41375-022-01615-z
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author Reiter, Andreas
Gotlib, Jason
Álvarez-Twose, Iván
Radia, Deepti H.
Lübke, Johannes
Bobbili, Priyanka J.
Wang, Aolin
Norregaard, Chelsea
Dimitrijevic, Saša
Sullivan, Erin
Louie-Gao, Melinda
Schwaab, Juliana
Galinsky, Ilene A.
Perkins, Cecelia
Sperr, Wolfgang R.
Sriskandarajah, Priya
Chin, Andi
Sendhil, Selvam R.
Duh, Mei Sheng
Valent, Peter
DeAngelo, Daniel J.
author_facet Reiter, Andreas
Gotlib, Jason
Álvarez-Twose, Iván
Radia, Deepti H.
Lübke, Johannes
Bobbili, Priyanka J.
Wang, Aolin
Norregaard, Chelsea
Dimitrijevic, Saša
Sullivan, Erin
Louie-Gao, Melinda
Schwaab, Juliana
Galinsky, Ilene A.
Perkins, Cecelia
Sperr, Wolfgang R.
Sriskandarajah, Priya
Chin, Andi
Sendhil, Selvam R.
Duh, Mei Sheng
Valent, Peter
DeAngelo, Daniel J.
author_sort Reiter, Andreas
collection PubMed
description Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER. Comparisons between outcomes of OS, duration of treatment (DOT), and maximum reduction in serum tryptase were conducted between the treatment cohorts, with adjustment for key covariates. The results indicated that the avapritinib cohort had significantly better survival (adjusted hazard ratio (HR) (95% confidence interval (CI)): 0.48 (0.29, 0.79); p = 0.004) and significantly longer DOT (HR: 0.36 (0.26, 0.51); p < 0.001) compared to the BAT cohort. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: −72.8, −47.9; p < 0.001). With no randomized controlled trials comparing avapritinib to BAT, these data offer crucial insights into the improved efficacy of avapritinib for the treatment of AdvSM.
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spelling pubmed-93432452022-08-03 Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis Reiter, Andreas Gotlib, Jason Álvarez-Twose, Iván Radia, Deepti H. Lübke, Johannes Bobbili, Priyanka J. Wang, Aolin Norregaard, Chelsea Dimitrijevic, Saša Sullivan, Erin Louie-Gao, Melinda Schwaab, Juliana Galinsky, Ilene A. Perkins, Cecelia Sperr, Wolfgang R. Sriskandarajah, Priya Chin, Andi Sendhil, Selvam R. Duh, Mei Sheng Valent, Peter DeAngelo, Daniel J. Leukemia Article Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER. Comparisons between outcomes of OS, duration of treatment (DOT), and maximum reduction in serum tryptase were conducted between the treatment cohorts, with adjustment for key covariates. The results indicated that the avapritinib cohort had significantly better survival (adjusted hazard ratio (HR) (95% confidence interval (CI)): 0.48 (0.29, 0.79); p = 0.004) and significantly longer DOT (HR: 0.36 (0.26, 0.51); p < 0.001) compared to the BAT cohort. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: −72.8, −47.9; p < 0.001). With no randomized controlled trials comparing avapritinib to BAT, these data offer crucial insights into the improved efficacy of avapritinib for the treatment of AdvSM. Nature Publishing Group UK 2022-07-05 2022 /pmc/articles/PMC9343245/ /pubmed/35790816 http://dx.doi.org/10.1038/s41375-022-01615-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Reiter, Andreas
Gotlib, Jason
Álvarez-Twose, Iván
Radia, Deepti H.
Lübke, Johannes
Bobbili, Priyanka J.
Wang, Aolin
Norregaard, Chelsea
Dimitrijevic, Saša
Sullivan, Erin
Louie-Gao, Melinda
Schwaab, Juliana
Galinsky, Ilene A.
Perkins, Cecelia
Sperr, Wolfgang R.
Sriskandarajah, Priya
Chin, Andi
Sendhil, Selvam R.
Duh, Mei Sheng
Valent, Peter
DeAngelo, Daniel J.
Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis
title Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis
title_full Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis
title_fullStr Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis
title_full_unstemmed Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis
title_short Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis
title_sort efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343245/
https://www.ncbi.nlm.nih.gov/pubmed/35790816
http://dx.doi.org/10.1038/s41375-022-01615-z
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