dc.contributor.author | Yang, JC-H | |
dc.contributor.author | Liu, G | |
dc.contributor.author | Lu, S | |
dc.contributor.author | He, J | |
dc.contributor.author | Burotto, M | |
dc.contributor.author | Ahn, M-J | |
dc.contributor.author | Kim, D-W | |
dc.contributor.author | Liu, X | |
dc.contributor.author | Zhao, Y | |
dc.contributor.author | Vincent, S | |
dc.contributor.author | Yin, J | |
dc.contributor.author | Ma, X | |
dc.contributor.author | Lin, HM | |
dc.contributor.author | Popat, S | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-11-08T11:33:50Z | |
dc.date.available | 2023-11-08T11:33:50Z | |
dc.date.issued | 2023-08-12 | |
dc.identifier | S1556-0864(23)00730-X | |
dc.identifier.citation | Journal of Thoracic Oncology, 2023, pp. S1556-0864(23)00730-X - | |
dc.identifier.issn | 1556-0864 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6049 | |
dc.identifier.eissn | 1556-1380 | |
dc.identifier.eissn | 1556-1380 | |
dc.identifier.doi | 10.1016/j.jtho.2023.08.010 | |
dc.identifier.doi | 10.1016/j.jtho.2023.08.010 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | S1556-0864(23)00730-X - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCIENCE INC | |
dc.relation.ispartof | Journal of Thoracic Oncology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Alectinib | |
dc.subject | Anaplastic lymphoma kinase | |
dc.subject | Brigatinib | |
dc.subject | Non–small cell lung cancer | |
dc.subject | Tyrosine kinase inhibitor | |
dc.title | Brigatinib Versus Alectinib in ALK-Positive NSCLC After Disease Progression on Crizotinib: Results of Phase 3 ALTA-3 Trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-08-07 | |
dc.date.updated | 2023-11-08T11:33:09Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.jtho.2023.08.010 | |
rioxxterms.licenseref.startdate | 2023-08-12 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37574132 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology/Thoracic Oncology (hon.) | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.jtho.2023.08.010 | |
dc.contributor.icrauthor | Popat, Sanjay | |
icr.provenance | Deposited by Mr Arek Surman on 2023-11-08. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S155608642300730X-main.pdf | |