Real-world treatment outcomes with brigatinib in patients with pretreated ALK+ metastatic non-small cell lung cancer.


Journal

Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805

Informations de publication

Date de publication:
07 2021
Historique:
received: 04 01 2021
revised: 08 04 2021
accepted: 12 05 2021
pubmed: 30 5 2021
medline: 25 6 2021
entrez: 29 5 2021
Statut: ppublish

Résumé

The next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC and in patients previously treated with crizotinib. A phase II trial showed that brigatinib is active in patients with ALK-positive metastatic NSCLC (mNSCLC) who had progressed on prior crizotinib (response rate 56 %, median PFS 16.7 months, median OS 34.1 months). We report final data from the UVEA-Brig study of brigatinib in ALK inhibitor-pretreated ALK-positive mNSCLC in clinical practice. UVEA-Brig was a retrospective chart review of patients treated with brigatinib in Italy, Norway, Spain and the UK in an expanded access program. Adults with ALK-positive mNSCLC, including those with brain lesions, resistant to or intolerant of ≥1 prior ALK inhibitor and ECOG performance status ≤3 were eligible. Patients received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The objectives were to describe patient characteristics, clinical disease presentation, treatment regimens used and clinical outcomes. Data for 104 patients (male: 43 %; median age: 53 [29-80] years; ECOG performance status 0/1/2/3: 41/41/10/5 %; brain/CNS metastases: 63 %) were analyzed. Patients had received a median of 2 (1-6) lines of systemic therapy prior to brigatinib (37.5 % received ≥3) and a median of 1 (1-5) lines of prior ALK inhibitor-containing therapy (crizotinib 83.6 %; ceritinib 50.0 %; alectinib 6.7 %; lorlatinib 4.8 %). At the time of analysis, 77 patients had discontinued brigatinib. Overall, the response rate was 39.8 %, median PFS was 11.3 (95 % CI:8.6-12.9) months and median OS was 23.3 (95 % CI: 16.0-NR) months. Four patients discontinued brigatinib treatment due to adverse events. 53 patients received systemic therapy after brigatinib, 42 with an ALK inhibitor (lorlatinib, n = 34). These real-world data indicate the activity and tolerability of brigatinib in patients with ALK-positive mNSCLC who were more heavily pretreated than patients included in clinical trials.

Sections du résumé

BACKGROUND
The next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC and in patients previously treated with crizotinib. A phase II trial showed that brigatinib is active in patients with ALK-positive metastatic NSCLC (mNSCLC) who had progressed on prior crizotinib (response rate 56 %, median PFS 16.7 months, median OS 34.1 months). We report final data from the UVEA-Brig study of brigatinib in ALK inhibitor-pretreated ALK-positive mNSCLC in clinical practice.
METHODS
UVEA-Brig was a retrospective chart review of patients treated with brigatinib in Italy, Norway, Spain and the UK in an expanded access program. Adults with ALK-positive mNSCLC, including those with brain lesions, resistant to or intolerant of ≥1 prior ALK inhibitor and ECOG performance status ≤3 were eligible. Patients received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The objectives were to describe patient characteristics, clinical disease presentation, treatment regimens used and clinical outcomes.
RESULTS
Data for 104 patients (male: 43 %; median age: 53 [29-80] years; ECOG performance status 0/1/2/3: 41/41/10/5 %; brain/CNS metastases: 63 %) were analyzed. Patients had received a median of 2 (1-6) lines of systemic therapy prior to brigatinib (37.5 % received ≥3) and a median of 1 (1-5) lines of prior ALK inhibitor-containing therapy (crizotinib 83.6 %; ceritinib 50.0 %; alectinib 6.7 %; lorlatinib 4.8 %). At the time of analysis, 77 patients had discontinued brigatinib. Overall, the response rate was 39.8 %, median PFS was 11.3 (95 % CI:8.6-12.9) months and median OS was 23.3 (95 % CI: 16.0-NR) months. Four patients discontinued brigatinib treatment due to adverse events. 53 patients received systemic therapy after brigatinib, 42 with an ALK inhibitor (lorlatinib, n = 34).
CONCLUSIONS
These real-world data indicate the activity and tolerability of brigatinib in patients with ALK-positive mNSCLC who were more heavily pretreated than patients included in clinical trials.

Identifiants

pubmed: 34051652
pii: S0169-5002(21)00397-4
doi: 10.1016/j.lungcan.2021.05.017
pii:
doi:

Substances chimiques

Organophosphorus Compounds 0
Protein Kinase Inhibitors 0
Pyrimidines 0
Anaplastic Lymphoma Kinase EC 2.7.10.1
brigatinib HYW8DB273J

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9-16

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Sanjay Popat (S)

Royal Marsden Hospital and The Institute of Cancer Research, London, UK. Electronic address: Sanjay.Popat@rmh.nhs.uk.

Odd Terje Brustugun (OT)

Section of Oncology, Drammen Hospital, Vestre Viken Hospital Trust, PO Box 800, N-3004, Drammen, Norway. Electronic address: ot.brustugun@gmail.com.

Jacques Cadranel (J)

Chest Department and Thoracic Oncology, AP-HP Hôpital Tenon and GRC#4 Theranoscan Sorbonne Université Paris, Service de Pneumologie et Oncologie Thoracique, Assistance Publique Hôpitaux de Paris, 4 rue de la Chine, Paris, 75970, France. Electronic address: jacques.cadranel@aphp.fr.

Enriqueta Felip (E)

Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron. Barcelona Hospital Campus, Passeig de la Vall d'Hebron, 119-129, 08035, Barcelona, Spain. Electronic address: efelip@vhio.net.

Marina Chiara Garassino (MC)

Division of Medical Oncology, Thoracic Oncology Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, Via Venezian, 1, 20126, Milan, Italy. Electronic address: mgarassino@medicine.bsd.uchicago.edu.

Frank Griesinger (F)

Department of Hematology and Oncology, University Dept. Internal Medicine-Oncology, Innere Medizin-Onkologie, Koordinator Cancer Center Oldenburg, Pius Hospital, University Medicine Oldenburg, Medizinischer Campus Universität Oldenburg, Georgstr. 12, D-26121, Oldenburg, Germany. Electronic address: Frank.Griesinger@Pius-Hospital.de.

Åslaug Helland (Å)

Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Department of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: ahelland@medisin.uio.no.

Maximilian Hochmair (M)

Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Department of Respiratory and Critical Care Medicine, Krankenhaus Nord, Klinik Floridsdorf, Brünnerstraße 68, A-1210, Vienna, Austria. Electronic address: maximilian.hochmair@gesundheitsverbund.at.

Maurice Pérol (M)

Medical Oncology Department, Léon Bérard Cancer Center, 28 Rue Laennec, 69008, Lyon, France. Electronic address: maurice.perol@lyon.unicancer.fr.

Nawal Bent-Ennakhil (N)

Takeda Pharmaceuticals International AG, Thurgauerstrasse 130, 8153, Opfikon, Switzerland. Electronic address: nawal.bentennakhil@takeda.com.

Christian Kruhl (C)

Takeda Pharmaceuticals International AG, Thurgauerstrasse 130, 8153, Opfikon, Switzerland. Electronic address: Christian.Kruhl@takeda.com.

Silvia Novello (S)

Oncology Department, University of Turin, AOU San Luigi, 10043, Orbassano, Turin, Italy. Electronic address: silvia.novello@unito.it.

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Classifications MeSH