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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorBauer, Todd
dc.contributor.authorShaw, Alice Tsang
dc.contributor.authorJohnson, Melissa L.
dc.contributor.authorNavarro Mendivil, Alejandro
dc.contributor.authorGainor, Justin F.
dc.contributor.authorThurm, Holger
dc.contributor.authorFelip Font, Enriqueta
dc.date.accessioned2021-10-26T07:11:19Z
dc.date.available2021-10-26T07:11:19Z
dc.date.issued2020-02
dc.identifier.citationBauer TM, Shaw AT, Johnson ML, Navarro A, Gainor JF, Thurm H, et al. Brain Penetration of Lorlatinib: Cumulative Incidences of CNS and Non-CNS Progression with Lorlatinib in Patients with Previously Treated ALK-Positive Non-Small-Cell Lung Cancer. Target Oncol. 2020 Feb;15:55–65.
dc.identifier.issn1776-260X
dc.identifier.urihttp://hdl.handle.net/11351/6462
dc.descriptionLorlatinib; Lung Cancer
dc.description.abstractBackground Lorlatinib is a potent, third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI) designed to penetrate the blood–brain barrier. Objective We report the cumulative incidence of central nervous system (CNS) and non-CNS progression with lorlatinib in patients with ALK-positive non-small-cell lung cancer (NSCLC) previously treated with ALK TKIs. Patients and methods In an ongoing phase II study (NCT01970865), 198 patients with ALK-positive NSCLC with ≥ 1 prior ALK TKI were enrolled into expansion cohorts (EXP) based on treatment history. Patients received lorlatinib 100 mg once daily. Patients were analyzed for progressive disease, categorized as CNS or non-CNS progression, by independent central review. Cumulative incidence probabilities were calculated adopting a competing risks approach. Results Fifty-nine patients received crizotinib as their only prior ALK TKI (EXP2–3A); cumulative incidence rates (CIRs) of CNS and non-CNS progression were both 22% at 12 months in patients with baseline CNS metastases (n = 37), and CIR of non-CNS progression at 12 months was higher versus that for CNS progression in patients without baseline CNS metastases [43% vs. 9% (n = 22)]. In patients who received ≥ 1 prior second-generation ALK TKI [EXP3B–5 (n = 139)], CIR of non-CNS progression at 12 months was higher versus that for CNS progression in patients both with and without baseline CNS metastases (35% vs. 23% (n = 94) and 55% vs. 12% (n = 45), respectively). Conclusions Lorlatinib showed substantial intracranial activity in patients with pretreated ALK-positive NSCLC, with or without baseline CNS metastases, whose disease progressed on crizotinib or second-generation ALK TKIs.
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofseriesTargeted Oncology;15
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectPulmons - Càncer - Tractament
dc.subjectAvaluació de resultats (Assistència sanitària)
dc.subject.meshCarcinoma, Non-Small-Cell Lung
dc.subject.mesh/drug therapy
dc.subject.meshDisease Progression
dc.titleBrain Penetration of Lorlatinib: Cumulative Incidences of CNS and Non-CNS Progression with Lorlatinib in Patients with Previously Treated ALK-Positive Non-Small-Cell Lung Cancer
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1007/s11523-020-00702-4
dc.subject.decscarcinoma de pulmón de células no pequeñas
dc.subject.decs/farmacoterapia
dc.subject.decsprogresión de la enfermedad
dc.relation.publishversionhttps://doi.org/10.1007/s11523-020-00702-4
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Bauer TM, Johnson ML] Sarah Cannon Cancer Research Institute/Tennessee Oncology, PLLC, 250 25th Ave N, Nashville, TN 37203, USA. [Shaw AT, Gainor JF] Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA. [Navarro A, Felip E] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Thurm H] Pfzer Oncology, 10777 Science Center Dr, La Jolla, CA, USA
dc.identifier.pmid32060867
dc.identifier.wos000514800300007
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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