{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:51:39Z","timestamp":1791301899010,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Transl Oncol"],"DOI":"10.1007\/s12094-026-04582-4","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:53:09Z","timestamp":1791298389000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-world evolution of first-line ALK-positive NSCLC management in Spain"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3503-4847","authenticated-orcid":false,"given":"Virginia","family":"Calvo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Zugazagoitia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Villa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Jos\u00e9","family":"Montes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"1","key":"4582_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s00408-025-00801-x","volume":"203","author":"H Jeon","year":"2025","unstructured":"Jeon H, Wang S, Song J, Gill H, Cheng H. Update 2025: Management of Non\u2011Small-Cell Lung Cancer. Lung. 2025 Mar 25;203(1):53.","journal-title":"Lung"},{"issue":"3","key":"4582_CR2","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1007\/s10278-023-00792-2","volume":"36","author":"J Lin","year":"2023","unstructured":"Lin J, Yu Y, Zhang X, Wang Z, Li S. Classifi cation of Histological Types and Stages in Non-small Cell Lung Cancer Using Radiomic Features Based on CT Images. J Digit Imaging. 2023 Jun;36(3):1029-1037.","journal-title":"J Digit Imaging"},{"key":"4582_CR3","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.critrevonc.2017.12.015","volume":"122","author":"A Addeo","year":"2018","unstructured":"Addeo A, Tabb\u00f2 F, Robinson T, Buff oni L, Novello S. Precision medicine in ALK rearranged NSCLC: A rapidly evolving scenario. Crit Rev Oncol Hematol. 2018 Feb;122:150-156.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"1","key":"4582_CR4","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1080\/07853890.2023.2187077","volume":"55","author":"M Gil","year":"2023","unstructured":"Gil M, Knetki-Wr\u00f3blewska M, Nizi\u0144ski P, Strzemski M, Krawczyk P. Eff ectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients. Ann Med. 2023 Dec;55(1):1018-1028.","journal-title":"Ann Med"},{"issue":"Suppl 3","key":"4582_CR5","doi-asserted-by":"publisher","first-page":"iii4","DOI":"10.1093\/annonc\/mdw301","volume":"27","author":"B Hallberg","year":"2016","unstructured":"Hallberg B, Palmer RH. The role of the ALK receptor in cancer biology. Ann Oncol. 2016 Sep;27 Suppl 3:iii4-iii15.","journal-title":"Ann Oncol"},{"issue":"3","key":"4582_CR6","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1007\/s11547-023-01602-z","volume":"128","author":"V Nardone","year":"2023","unstructured":"Nardone V, Romeo C, D'Ippolito E, Pastina P, D'Apolito M, Pirtoli L, et al. The role of brain radiotherapy for EGFR-and ALK-positive non-small-cell lung cancer with brain metastases: a review. Radiol Med. 2023 Mar;128(3):316-329.","journal-title":"Radiol Med"},{"issue":"13","key":"4582_CR7","doi-asserted-by":"publisher","first-page":"e510","DOI":"10.1016\/S1470-2045(15)00013-3","volume":"16","author":"I Zhang","year":"2015","unstructured":"Zhang I, Zaorsky NG, Palmer JD, Mehra R, Lu B. Targeting brain metastases in ALK-rearranged non-small-cell lung cancer. Lancet Oncol. 2015 Oct;16(13):e510-21.","journal-title":"Lancet Oncol"},{"issue":"3","key":"4582_CR8","doi-asserted-by":"publisher","first-page":"200","DOI":"10.3390\/medsci13030200","volume":"13","author":"W Shalata","year":"2025","unstructured":"Shalata W, Naamneh R, Najjar W, Abu Amna M, Asla M, Agbarya A, et al. Effi cacy of Tyrosine Kinase Inhibitors in ALK and EGFR-Mutated Non-Small Cell Lung Cancer with Brain Metastases. Med Sci (Basel). 2025 Sep 18;13(3):200.","journal-title":"Med Sci (Basel)"},{"issue":"12","key":"4582_CR9","doi-asserted-by":"publisher","first-page":"996","DOI":"10.3390\/cimb47120996","volume":"47","author":"Y-K Zhang","year":"2025","unstructured":"Zhang YK, Tong JB, Luo MX, Qin ZP, Wang R. ALK-Targeted Therapy: Resistance Mechanisms and Emerging Precision Strategies. Curr Issues Mol Biol. 2025 Nov 27;47(12):996.","journal-title":"Curr Issues Mol Biol"},{"issue":"4","key":"4582_CR10","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1093\/annonc\/mdx121","volume":"29","author":"F Blackhall","year":"2018","unstructured":"Blackhall F, Cappuzzo F. Crizotinib: from discovery to accelerated development to front-line treatment. Ann Oncol. 2018 Apr 1;29(4):1073. doi: 10.1093\/annonc\/mdx121. Erratum for: Ann Oncol. 2016 Sep;27 Suppl 3:iii35-iii41.","journal-title":"Ann Oncol"},{"issue":"15","key":"4582_CR11","doi-asserted-by":"publisher","first-page":"e443","DOI":"10.1200\/JCO.2010.34.1313","volume":"29","author":"DB Costa","year":"2011","unstructured":"Costa DB, Kobayashi S, Pandya SS, Yeo WL, Shen Z, Tan W, Wilner KD. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol. 2011 May 20;29(15):e443-5.","journal-title":"J Clin Oncol"},{"key":"4582_CR12","doi-asserted-by":"publisher","first-page":"18","DOI":"10.17925\/EOH.2020.16.1.18","volume":"16","author":"M Aldea","year":"2020","unstructured":"Aldea M, Besse B, Hendriks L. ALK inhibitors in ALK-positive NSCLC with central nervous system metastases. Eur Oncol Haematol. 2020;16:18-21.","journal-title":"Eur Oncol Haematol"},{"issue":"18","key":"4582_CR13","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1056\/NEJMoa1007478","volume":"363","author":"YL Choi","year":"2010","unstructured":"Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, et al. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010;363(18):1734-1739.","journal-title":"N Engl J Med"},{"issue":"10","key":"4582_CR14","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1158\/2159-8290.CD-16-0596","volume":"6","author":"JF Gainor","year":"2016","unstructured":"Gainor JF, Dardaei L, Yoda S, Friboulet L, Leshchiner I, Katayama R, et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer. Cancer Discov. 2016;6(10):1118-1133.","journal-title":"Cancer Discov"},{"issue":"12","key":"4582_CR15","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1016\/S1470-2045(18)30649-1","volume":"19","author":"BJ Solomon","year":"2018","unstructured":"Solomon BJ, Besse B, Bauer TM, Felip E, Soo RA, Camidge DR, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018;19(12):1654-1667.","journal-title":"Lancet Oncol"},{"issue":"12","key":"4582_CR16","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1016\/S1470-2045(17)30680-0","volume":"18","author":"AT Shaw","year":"2017","unstructured":"Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017;18(12):1590-1599.","journal-title":"Lancet Oncol"},{"issue":"6","key":"4582_CR17","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1158\/2159-8290.CD-17-1256","volume":"8","author":"S Yoda","year":"2018","unstructured":"Yoda S, Lin JJ, Lawrence MS, Burke BJ, Friboulet L, Langenbucher A, et al. Sequential ALK inhibitors can select for lorlatinib-resistant compound ALK mutations in ALK-positive lung cancer. Cancer Discov. 2018;8(6):714-729.","journal-title":"Cancer Discov"},{"issue":"21","key":"4582_CR18","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1056\/NEJMoa2027187","volume":"383","author":"AT Shaw","year":"2020","unstructured":"Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, et al. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med. 2020;383(21):2018-2029.","journal-title":"N Engl J Med"},{"issue":"29","key":"4582_CR19","doi-asserted-by":"publisher","first-page":"3400","DOI":"10.1200\/JCO.24.00581","volume":"42","author":"BJ Solomon","year":"2024","unstructured":"Solomon BJ, Bauer TM, Mok TSK, Liu G, Soo RA, Mazieres J, et al. Lorlatinib versus crizotinib in patients with advanced ALK-positive non-small-cell lung cancer: 5-year outcomes from the phase III CROWN study. J Clin Oncol. 2024;42(29):3400-3409.","journal-title":"J Clin Oncol"},{"issue":"2","key":"4582_CR20","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.jtho.2024.10.018","volume":"20","author":"HJ Hoe","year":"2025","unstructured":"Hoe HJ, Solomon BJ. Based on the CROWN fi ndings, lorlatinib should be the preferred first-line treatment for patients with advanced ALK-positive NSCLC. J Thorac Oncol. 2025;20(2):154-156.","journal-title":"J Thorac Oncol"},{"key":"4582_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2025.108680","author":"M Provencio","year":"2025","unstructured":"Provencio M, Cobo M, Rodriguez-Abreu D, Carcereny E, Calvo V, L\u00f3pez Castro R, et al. Biomarker landscape in advanced NSCLC: insights from a national prospective registry. Lung Cancer. 2025;207:108680.https:\/\/doi.org\/10.1016\/j.lungcan.2025.108680.","journal-title":"Lung Cancer"},{"key":"4582_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.863461","volume":"12","author":"L Peng","year":"2022","unstructured":"Peng L, Zhu L, Sun Y, Stebbing J, Selvaggi G, Zhang Y, Yu Z. Targeting ALK rearrangements in NSCLC: current state of the art. Front Oncol. 2022;12:863461.","journal-title":"Front Oncol"},{"issue":"1","key":"4582_CR23","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1186\/s12967-024-05388-0","volume":"22","author":"L Wu","year":"2024","unstructured":"Wu L, Zou Z, Li Y, Hao X, Ying J, Li J, Xing P. Progression patterns, resistant mechanisms and subsequent therapy for ALK-positive NSCLC in the era of second-generation ALK-TKIs. J Transl Med. 2024;22(1):585.","journal-title":"J Transl Med"},{"issue":"9","key":"4582_CR24","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1056\/NEJMoa1704795","volume":"377","author":"S Peters","year":"2017","unstructured":"Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377(9):829-838.","journal-title":"N Engl J Med"},{"issue":"12","key":"4582_CR25","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1016\/j.jtho.2021.07.035","volume":"16","author":"DR Camidge","year":"2021","unstructured":"Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Lee JS, et al. Brigatinib versus crizotinib in ALK inhibitor-naive advanced ALK-positive NSCLC: final results of phase 3 ALTA-1L trial. J Thorac Oncol. 2021;16(12):2091-2108.","journal-title":"J Thorac Oncol"},{"key":"4582_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/medsci13030200","author":"W Shalata","year":"2025","unstructured":"Shalata W, Naamneh R, Najjar W, Abu Amna M, Asla M, Agbarya A, Brenner R, Abu Jama A, Abu Yasin N, Abu Juda M, Abu Zeid EED, Rouvinov K, Yakobson A. Effi cacy of Tyrosine Kinase Inhibitors in ALK and EGFR-Mutated Non-Small Cell Lung Cancer with Brain Metastases. Med Sci (Basel). 2025 Sep 18;13(3):200https:\/\/doi.org\/10.3390\/medsci13030200.","journal-title":"Med Sci"},{"key":"4582_CR27","doi-asserted-by":"publisher","DOI":"10.21037\/pcm-23-18","author":"F Facchinetti","year":"2024","unstructured":"Facchinetti F, et al. ALK fusions turn sixteen in lung cancer: a review on their biology, detection and therapy. Precis Cancer Med. 2024;6.https:\/\/doi.org\/10.21037\/pcm-23-18.","journal-title":"Precis Cancer Med"},{"issue":"9","key":"4582_CR28","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41568-019-0179-8","volume":"19","author":"F Skoulidis","year":"2019","unstructured":"Skoulidis F, Heymach JV. Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat Rev Cancer. 2019;19(9):495-509.","journal-title":"Nat Rev Cancer"},{"issue":"8","key":"4582_CR29","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1016\/j.jtho.2023.03.020","volume":"18","author":"SP de Leeuw","year":"2023","unstructured":"de Leeuw SP, et al. Analysis of serious weight gain in patients using alectinib for ALK-positive lung cancer. J Thorac Oncol. 2023;18(8):1017-1030.","journal-title":"J Thorac Oncol"},{"issue":"10","key":"4582_CR30","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1016\/j.jtho.2018.07.004","volume":"13","author":"A Drilon","year":"2018","unstructured":"Drilon A, Hu ZI, Lai GGY, Tan DSW. Frequency of brain metastases and multikinase inhibitor outcomes in patients with RET-rearranged lung cancers. J Thorac Oncol. 2018;13(10):1595-1601.","journal-title":"J Thorac Oncol"},{"issue":"1","key":"4582_CR31","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.lungcan.2015.01.020","volume":"88","author":"D Rangachari","year":"2015","unstructured":"Rangachari D, Yamaguchi N, VanderLaan PA, Folch E, Mahadevan A, Floyd SR, et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer. 2015;88(1):108-111.","journal-title":"Lung Cancer"},{"issue":"8","key":"4582_CR32","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/j.annonc.2020.04.478","volume":"31","author":"T Mok","year":"2020","unstructured":"Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056-1064.","journal-title":"Ann Oncol"}],"container-title":["Clinical and Translational Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12094-026-04582-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12094-026-04582-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12094-026-04582-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:53:10Z","timestamp":1791298390000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12094-026-04582-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":32,"alternative-id":["4582"],"URL":"https:\/\/doi.org\/10.1007\/s12094-026-04582-4","relation":{},"ISSN":["1699-3055"],"issn-type":[{"value":"1699-3055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"assertion":[{"value":"18 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Virginia Calvo de Juan has received research funding from Roche; has participated in advisory boards and\/or received honoraria for lectures from Roche, AstraZeneca, MSD, Bristol Myers Squibb (BMS), Takeda, Regeneron, Amgen, Pfizer, GlaxoSmithKline (GSK), Boehringer Ingelheim, Johnson & Johnson, BeiGene, and Pierre Fabre; and has received travel support from AstraZeneca, Roche, MSD, Takeda, Johnson & Johnson, BeiGene, and Pfizer. Jon Zugazagoitia reports speaker, advisory, or travel honoraria from Lilly, PharmaMar, Amgen, Boehringer Ingelheim, Johnson & Johnson, Pierre Fabre, Takeda, Sanofi, Bristol Myers Squibb (BMS), AstraZeneca, MSD, Roche, Pfizer, and Novartis, and research support\/grants from Johnson & Johnson, Pfizer, and AstraZeneca. Elisabet Garcia, Gerardo Villa, and Antonio Jos\u00e9 Montes are employees of Pfizer.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No ethics approval was required as the data were anonymized and collected in routine clinical practice.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":4,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}}]}}