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

Autor: Gerson Peltz, Melissa Lynne Johnson, Enriqueta Felip, Todd M. Bauer, Yazdi K. Pithavala, Holger Thurm, Alice T. Shaw, Alejandro Navarro, Justin F. Gainor, Antonello Abbattista
Přispěvatelé: Institut Català de la Salut, [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, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
Lung Neoplasms
Phases of clinical research
Aminopyridines
Other subheadings::Other subheadings::/drug therapy [Other subheadings]
Tyrosine-kinase inhibitor
0302 clinical medicine
hemic and lymphatic diseases
Carcinoma
Non-Small-Cell Lung
Pharmacology (medical)
Cumulative incidence
Original Research Article
Aged
80 and over
Brain Neoplasms
Incidence
Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma
Bronchogenic::Carcinoma
Non-Small-Cell Lung [DISEASES]
Middle Aged
afecciones patológicas
signos y síntomas::procesos patológicos::atributos de la enfermedad::progresión de la enfermedad [ENFERMEDADES]
030220 oncology & carcinogenesis
Disease Progression
Female
medicine.drug
Adult
medicine.medical_specialty
Lactams
medicine.drug_class
Lactams
Macrocyclic
Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores]
03 medical and health sciences
Internal medicine
medicine
ROS1
Humans
Pathological Conditions
Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression [DISEASES]
Lung cancer
Aged
Crizotinib
business.industry
neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES]
medicine.disease
Lorlatinib
respiratory tract diseases
030104 developmental biology
Avaluació de resultats (Assistència sanitària)
Pyrazoles
business
Pulmons - Càncer - Tractament
Progressive disease
Zdroj: Targeted Oncology
Scientia
ISSN: 1776-260X
Popis: Background 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. ClinicalTrials.gov identifier NCT01970865. Electronic supplementary material The online version of this article (10.1007/s11523-020-00702-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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