dc.date.accessioned | 2023-01-09T18:02:38Z | |
dc.date.available | 2023-01-09T18:02:38Z | |
dc.date.created | 2022-05-11T13:25:58Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Wolf, J. Helland, Åslaug Oh, I.-J. Migliorino, M.R. Dziadziuszko, R. Wrona, A. de Castro, Castro Mazieres, J. Griesinger, F. Chlistalla, M. Cardona, A. Ruf, T. Trunzer, K. Smoljanovic, V. Novello, S. . Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer. ESMO Open. 2022, 7(1) | |
dc.identifier.uri | http://hdl.handle.net/10852/98589 | |
dc.description.abstract | Background
At the primary data cut-off, the ALUR study demonstrated significantly improved progression-free survival (PFS) and central nervous system (CNS) objective response rate (ORR) with alectinib versus chemotherapy in pretreated, advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. We report final efficacy and safety data, and exploratory molecular profiling.
Patients and methods
Patients who received prior platinum-doublet chemotherapy and crizotinib were randomized 2 : 1 to receive alectinib 600 mg twice daily (n = 79) or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, every 3 weeks; n = 40) until progressive disease, death or withdrawal. The primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, CNS ORR and safety. Plasma samples were collected at baseline, then every 6 weeks until progressive disease; molecular factors detected by next-generation sequencing were correlated with outcomes.
Results
Investigator-assessed PFS was significantly longer with alectinib than chemotherapy (median 10.9 versus 1.4 months; hazard ratio 0.20, 95% confidence interval 0.12-0.33; P < 0.001). ORR was 50.6% with alectinib versus 2.5% with chemotherapy (P < 0.001). In patients with measurable CNS metastases at baseline, CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples. Confirmed partial responses were observed with alectinib in 6/11 patients with a secondary ALK mutation and 4/6 patients with a non-EML4-ALK (where EML4 is echinoderm microtubule-associated protein-like 4) fusion. Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93).
Conclusions
Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53. | |
dc.language | EN | |
dc.publisher | BMJ | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer | |
dc.title.alternative | ENEngelskEnglishFinal efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer | |
dc.type | Journal article | |
dc.creator.author | Wolf, J. | |
dc.creator.author | Helland, Åslaug | |
dc.creator.author | Oh, I.-J. | |
dc.creator.author | Migliorino, M.R. | |
dc.creator.author | Dziadziuszko, R. | |
dc.creator.author | Wrona, A. | |
dc.creator.author | de Castro, Castro | |
dc.creator.author | Mazieres, J. | |
dc.creator.author | Griesinger, F. | |
dc.creator.author | Chlistalla, M. | |
dc.creator.author | Cardona, A. | |
dc.creator.author | Ruf, T. | |
dc.creator.author | Trunzer, K. | |
dc.creator.author | Smoljanovic, V. | |
dc.creator.author | Novello, S. | |
cristin.unitcode | 185,53,49,12 | |
cristin.unitname | Kreftforskning | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 2023573 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=ESMO Open&rft.volume=7&rft.spage=&rft.date=2022 | |
dc.identifier.jtitle | ESMO Open | |
dc.identifier.volume | 7 | |
dc.identifier.issue | 1 | |
dc.identifier.pagecount | 0 | |
dc.identifier.doi | https://doi.org/10.1016/j.esmoop.2021.100333 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2059-7029 | |
dc.type.version | PublishedVersion | |
cristin.articleid | 100333 | |