{ "abstract": "BACKGROUND: Due to the unprecedented progression-free survival (PFS) benefit with lorlatinib after 5 years of follow-up in the phase III CROWN study, we aimed to quantify long-term outcomes at 7 years. PATIENTS AND METHODS: Treatment-naive patients (N = 296) with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) were randomly assigned 1:1 to receive lorlatinib 100 mg once a day (n = 149) or crizotinib 250 mg twice a day (n = 147). This post hoc analysis presents investigator-assessed efficacy outcomes, safety, and biomarker analyses. RESULTS: With a median follow-up of 83.0 and 77.2 months, median PFS was not reached (NR) with lorlatinib [95% confidence interval (CI), 68.5-NR] and was 9.1 months (95% CI 7.4-10.9) with crizotinib [hazard ratio (HR) 0.19, 95% CI 0.13-0.26]; 7-year PFS was 55% and 3%, respectively. With lorlatinib, patients without a PFS event at the end of 24 months had a 79% probability of survival without progression at year 7. No new intracranial progression events occurred after the first 30 months on lorlatinib. Median time to intracranial progression was NR (95% CI NR-NR) with lorlatinib and 16.4 months (95% CI 12.7-21.9) with crizotinib (HR 0.06, 95% CI 0.03-0.12). Overall survival follow-up is ongoing; the number of events for a protocol-specified analysis has not been met. The safety profile was consistent with the 5-year results. With lorlatinib, treatment-related adverse events did not lead to discontinuations after the first 26 months. More genetic alterations were detected in circulating tumor DNA samples from early progressors than in long-term responders on lorlatinib; new potential resistance mechanisms were identified. CONCLUSIONS: With median PFS yet to be reached after 7 years of follow-up in CROWN, lorlatinib continues to show unprecedented long-term benefit in patients with advanced ALK-positive NSCLC. Patients without progression within 24 months on lorlatinib have a low risk of progression or death at year 7 and may continue long-term treatment. Findings suggest that sustained long-term disease control with first-line lorlatinib may enable advanced ALK-positive NSCLC to evolve toward a chronic condition.", "abstract_shown": true, "affiliations": [ "Department of Medical Oncology, Dana-Farber Cancer Institute and Massachusetts General Hospital Cancer Center, Boston, USA. Electronic address: alice_shaw@dfci.harvard.edu", "Department of Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia", "Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain", "Tennessee Oncology, PLLC, Greco-Hainsworth Centers for Research, Nashville, USA", "Princess Margaret Cancer Centre, University Health Network, Toronto, Canada", "Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan", "Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, China", "Department of Haematology-Oncology, National University Cancer Institute, Singapore", "Thoracic Oncology Department, Toulouse University Hospital, Toulouse, France", "Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea", "Translational Oncology, Pfizer, La Jolla, USA", "Oncology Drug Development, Pfizer, Milan, Italy", "Oncology Lung Cancer, Pfizer, Paris, France", "Department of Clinical Oncology, State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong Special Administrative Region of China, China" ], "article_type": null, "arxiv": null, "author_total": 16, "authors": [ { "affs": [ 0 ], "name": "Alice Tsang Shaw", "orcid": "0000-0001-6337-1093" }, { "affs": [ 1 ], "name": "Benjamin Solomon", "orcid": "0000-0003-3059-5730" }, { "affs": [ 2 ], "name": "Enriqueta Felip", "orcid": "0000-0002-7620-0098" }, { "affs": [ 3 ], "name": "Todd Michael Bauer", "orcid": "0000-0002-3078-5043" }, { "affs": [ 4 ], "name": "G. Liu" }, { "affs": [ 5 ], "name": "Y. Goto", "orcid": "0000-0002-7437-5054" }, { "affs": [ 6 ], "name": "Yan Wu", "orcid": "0000-0002-3611-0258" }, { "affs": [ 7 ], "name": "R.A. Soo", "orcid": "0000-0002-3053-3997" }, { "affs": [ 8 ], "name": "Julien Mazières", "orcid": "0000-0002-5921-7613" }, { "affs": [ 9 ], "name": "D G Kim", "orcid": "0000-0001-5124-7132" }, { "affs": [ 10 ], "name": "I.‐M. Wang", "orcid": "0000-0001-9414-0394" }, { "affs": [ 11 ], "name": "Jolanda Paolini", "orcid": "0000-0003-2711-5302" }, { "affs": [ 11 ], "name": "Anna Polli" }, { "affs": [ 12 ], "name": "N. Rifi", "orcid": "0009-0004-7627-9519" }, { "affs": [ 11 ], "name": "Francesca Toffalorio", "orcid": "0009-0006-1368-9347" }, { "affs": [ 13 ], "name": "T.S.K. Mok" } ], "bibtex": "https://research.draconitic.com/paper/dcs2wpbm78vzh.bib", "cited_by": 20, "doi": "10.1016/j.annonc.2026.05.692", "fulltext_url": null, "id": "dcs2wpbm78vzh", "issns": [ "0923-7534", "1569-8041" ], "landing_url": "https://doi.org/10.1016/j.annonc.2026.05.692", "language": "en", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2740|Lung Cancer Treatments and Mutations" ] ], "openalex": "W7162771098", "pdf_url": "https://www.annalsofoncology.org/article/S0923-7534(26)00876-8/pdf", "pmcid": null, "pmid": "42217582", "published": "2026-05-29", "publisher": "Elsevier BV", "ris": "https://research.draconitic.com/paper/dcs2wpbm78vzh.ris", "sources": [ { "first_seen": "2026-10-30T13:26:54Z", "native_id": "W7162771098", "source": "openalex", "url": "https://doi.org/10.1016/j.annonc.2026.05.692" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2740|Lung Cancer Treatments and Mutations", "subfield": "general" } ], "title": "Lorlatinib versus crizotinib as first-line treatment for advanced ALK-positive non-small-cell lung cancer: 7-year update from the phase III CROWN study", "title_text": "Lorlatinib versus crizotinib as first-line treatment for advanced ALK-positive non-small-cell lung cancer: 7-year update from the phase III CROWN study", "type": "peer-reviewed", "updated_at": "2026-11-04T13:21:13Z", "url": "https://research.draconitic.com/paper/dcs2wpbm78vzh", "venue": "Annals of Oncology", "versions": [] }