Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib : Results of Phase 3 ALTA-3 Trial
Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved..
INTRODUCTION: This open-label, phase 3 trial (ALTA-3; NCT03596866) compared efficacy and safety of brigatinib versus alectinib for ALK+ NSCLC after disease progression on crizotinib.
METHODS: Patients with advanced ALK+ NSCLC that progressed on crizotinib were randomized 1:1 to brigatinib 180 mg once daily (7-d lead-in, 90 mg) or alectinib 600 mg twice daily, aiming to test superiority. The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Interim analysis for efficacy and futility was planned at approximately 70% of 164 expected PFS events.
RESULTS: The population (N = 248; brigatinib, n = 125; alectinib, n = 123) was notable for long median duration of prior crizotinib (16.0-16.8 mo) and low rate of ALK fusion in baseline circulating tumor DNA (ctDNA; 78 of 232 [34%]). Median blinded independent review committee-assessed PFS was 19.3 months with brigatinib and 19.2 months with alectinib (hazard ratio = 0.97 [95% confidence interval: 0.66-1.42], p = 0.8672]). The study met futility criterion. Overall survival was immature (41 events [17%]). Exploratory analyses pooled across the treatment groups revealed median PFS of 11.1 versus 22.5 months in patients with versus without ctDNA-detectable ALK fusion at baseline (hazard ratio: 0.48 [95% confidence interval: 0.32-0.71]). Treatment-related adverse events in more than 30% of patients (brigatinib, alectinib) were elevated levels of blood creatine phosphokinase (70%, 29%), aspartate aminotransferase (53%, 38%), and alanine aminotransferase (40%, 36%).
CONCLUSIONS: Brigatinib was not superior to alectinib for PFS in crizotinib-pretreated ALK+ NSCLC. Safety was consistent with the well-established and unique profiles of each drug. The low proportion of patients with ctDNA-detectable ALK fusion may account for prolonged PFS with both drugs in ALTA-3.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer - 18(2023), 12 vom: 14. Dez., Seite 1743-1755 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, James Chih-Hsin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.11.2023 Date Revised 27.12.2023 published: Print-Electronic ClinicalTrials.gov: NCT03596866 Citation Status MEDLINE |
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| doi: |
10.1016/j.jtho.2023.08.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360736211 |
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| 100 | 1 | |a Yang, James Chih-Hsin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib |b Results of Phase 3 ALTA-3 Trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 27.11.2023 | ||
| 500 | |a Date Revised 27.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03596866 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a INTRODUCTION: This open-label, phase 3 trial (ALTA-3; NCT03596866) compared efficacy and safety of brigatinib versus alectinib for ALK+ NSCLC after disease progression on crizotinib | ||
| 520 | |a METHODS: Patients with advanced ALK+ NSCLC that progressed on crizotinib were randomized 1:1 to brigatinib 180 mg once daily (7-d lead-in, 90 mg) or alectinib 600 mg twice daily, aiming to test superiority. The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Interim analysis for efficacy and futility was planned at approximately 70% of 164 expected PFS events | ||
| 520 | |a RESULTS: The population (N = 248; brigatinib, n = 125; alectinib, n = 123) was notable for long median duration of prior crizotinib (16.0-16.8 mo) and low rate of ALK fusion in baseline circulating tumor DNA (ctDNA; 78 of 232 [34%]). Median blinded independent review committee-assessed PFS was 19.3 months with brigatinib and 19.2 months with alectinib (hazard ratio = 0.97 [95% confidence interval: 0.66-1.42], p = 0.8672]). The study met futility criterion. Overall survival was immature (41 events [17%]). Exploratory analyses pooled across the treatment groups revealed median PFS of 11.1 versus 22.5 months in patients with versus without ctDNA-detectable ALK fusion at baseline (hazard ratio: 0.48 [95% confidence interval: 0.32-0.71]). Treatment-related adverse events in more than 30% of patients (brigatinib, alectinib) were elevated levels of blood creatine phosphokinase (70%, 29%), aspartate aminotransferase (53%, 38%), and alanine aminotransferase (40%, 36%) | ||
| 520 | |a CONCLUSIONS: Brigatinib was not superior to alectinib for PFS in crizotinib-pretreated ALK+ NSCLC. Safety was consistent with the well-established and unique profiles of each drug. The low proportion of patients with ctDNA-detectable ALK fusion may account for prolonged PFS with both drugs in ALTA-3 | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Alectinib | |
| 650 | 4 | |a Anaplastic lymphoma kinase | |
| 650 | 4 | |a Brigatinib | |
| 650 | 4 | |a Non–small cell lung cancer | |
| 650 | 4 | |a Tyrosine kinase inhibitor | |
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| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 700 | 1 | |a Liu, Geoffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shun |e verfasserin |4 aut | |
| 700 | 1 | |a He, Jianxing |e verfasserin |4 aut | |
| 700 | 1 | |a Burotto, Mauricio |e verfasserin |4 aut | |
| 700 | 1 | |a Ahn, Myung-Ju |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Dong-Wan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, XiaoQing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yanqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Vincent, Sylvie |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Jiani |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Huamao M |e verfasserin |4 aut | |
| 700 | 1 | |a Popat, Sanjay |e verfasserin |4 aut | |
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