Brigatinib (Alunbrig®) is an oral, potent and selective anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor approved for treating adults with advanced ALK-positive non-small-cell lung cancer (NSCLC) not previously treated with an ALK inhibitor. In a multinational, phase III study (ALTA-1L) in this patient population, brigatinib significantly improved median blinded independent review committee-assessed progression-free survival (PFS), the confirmed objective response (OR) rate and the confirmed intracranial OR rate compared with crizotinib. Its tolerability profile in this study was manageable and no new safety concerns were identified. Although final analysis data are awaited with interest, brigatinib therapy extends the first-line treatment options available for standard of care in this patient population, including patients with CNS metastases.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Camidge DR, Doebele RC. Treating ALK-positive lung cancer: early successes and future challenges. Nat Rev Clin Oncol. 2012;9(5):268–77.
Cao Z, Gao Q, Fu M, et al. Anaplastic lymphoma kinase fusions: roles in cancer and therapeutic perspectives. Oncol Lett. 2019;17(2):2020–30.
National Comprehensive Cancer Network. NCCN guidelines version 8.2020 non-small-cell lung cancer. 2020. https://www.nccn.org. Accessed 17 Sep 2020.
Shaw AT, Engelman JA. ALK in lung cancer: past, present, and future. J Clin Oncol. 2013;31(8):1105–11.
Frampton JE. Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer. Drugs. 2013;73(18):2031–51.
Shi W, Dicker AP. CNS metastases in patients with non-small-cell lung cancer and ALK gene rearrangement. J Clin Oncol. 2016;34(2):107–9.
Markham A. Brigatinib: first global approval. Drugs. 2017;77(10):1131–5.
Zhang S, Anjum R, Squillace R, et al. The potent ALK inhibitor brigatinib (AP26113) overcomes mechanisms of resistance to first- and second-generation ALK inhibitors in preclinical models. Clin Cancer Res. 2016;22(22):5527–38.
Takeda Pharmaceutical Company Limited. ALUNBRIG® (brigatinib) tablets, for oral use: US prescribing information. 2020. https://www.fda.gov/. Accessed 10 Jun 2020.
Gettinger SN, Bazhenova LA, Langer CJ, et al. Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial. Lancet Oncol. 2016;17(12):1683–96.
Kim DW, Tiseo M, Ahn MJ, et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol. 2017;35(22):2490–8.
Ng TL, Narasimhan N, Gupta N, et al. Early-onset pulmonary events associated with brigatinib use in advanced NSCLC. J Thorac Oncol. 2020;15(7):1190–9.
Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018;379(21):2027–39.
Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L trial. J Clin Oncol. 2020. https://doi.org/10.1200/JCO.20.00505.
Takeda Pharma. Alunbrig film-coated tablets: EU summary of product characteristics. 2020. https://www.ema.europa.eu/. Accessed 12 Jun 2020.
Tugnait M, Gupta N, Hanley MJ, et al. The effect of a high-fat meal on the pharmacokinetics of brigatinib, an oral anaplastic lymphoma kinase inhibitor, in healthy volunteers. Clin Pharmacol Drug Dev. 2019;8(6):734–41.
Gupta N, Reckamp K, Camidge D, et al. Population pharmacokinetic (PK) and exposure-response analyses from the pivotal ALTA-1L study: model-based analyses supporting the brigatinib dose in patients with anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) [abstract no. e21725]. J Clin Oncol. 2020;38(15 Suppl).
Ahn MJ, Kim HR, Yang JCH, et al. Brigatinib (BRG) versus crizotinib (CRZ) in Asian versus non-Asian patients (pts) in the phase III ALTA-1L trial [abstract no. 9026]. J Clin Oncol. 2019;37(Suppl 15).
Ahn M, Kim HR, Yang JC, et al. Brigatinib (BRG) vs crizotinib (CRZ) in Asian vs non-Asian patients (pts): update from ALTA-1L [abstract no. 1304P]. Ann Oncol. 2020;31(Suppl 4):S754–840.
Camidge DR, Niu H, Kim HR, et al. Correlation of baseline molecular and clinical variables with ALK inhibitor efficacy in ALTA-1L [abstract no 9517]. J Clin Oncol. 2020;38(15 Suppl).
European Medicines Agency. Brigatinib: CHMP extension of indication variation assessment report. 2020. https://www.ema.europa.eu/. Accessed 7 Sep 2020.
Campelo RG, Lin HM, Perol M, et al. Health-related quality of life (HRQoL) results from ALTA-1L: phase 3 study of brigatinib vs crizotinib as first-line (1L) ALK therapy in advanced ALK+ nonsmall cell lung cancer (NSCLC) [abstract no. 9084]. J Clin Oncol. 2019;37(Suppl 15).
Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2020. https://www.esmo.org/. Accessed 25 Sep 2020.
National Institute for Health and Care Excellence. Brigatinib for ALK-positive advanced non-small-cell lung cancer that has not been previously treated with an ALK inhibitor. Final appraisal document. https://www.nice.org.uk/. Accessed 14 Dec 2020.
Genentech USA Inc. ALECENSA® (alectinib) capsules, for oral use: US prescribing information. 2018. https://www.fda.gov/. Accessed 13 Nov 2020.
Roche Registration GmbH. Alecensa 150 mg hard capsules: EU summary of product characteristics. 2020. https://www.ema.europa.eu/. Accessed 13 Nov 2020.
Novartis Pharmaceuticals Corporation. ZYKADIA® (ceritinib) tablets, for oral use: US prescribing information. 2019. https://www.fda.gov/. Accessed 13 Nov 2020.
Novartis Pharma GmbH. Zykadia 150 mg hard capsules: EU summary of product characteristics. 2020. https://www.ema.europa.eu/. Accessed 13 Nov 2020.
During the peer review process, the manufacturer of the agent under review was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
The preparation of this review was not supported by any external funding.
Authorship and conflict of interest
Sheridan Hoy is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.
Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability
The manuscript was reviewed by: K. Araki, Department of Medical Oncology, Gunma Prefectural Cancer Center, Ohta, Japan; R. Califano, Department of Medical Oncology, The Christie NHS Foundation Trust and Division of Cancer Sciences, The University of Manchester, Manchester, UK; R. Descourt, Oncology Department, Centre Hospitalier Universitaire, Brest, France; A. Russo, Medical Oncology Unit, A.O. Papardo, Messina, Italy.
About this article
Cite this article
Hoy, S.M. Brigatinib: A Review in ALK-Inhibitor Naïve Advanced ALK-Positive NSCLC. Drugs (2021). https://doi.org/10.1007/s40265-020-01449-y