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¹ Trakya University, Faculty of Medicine, Department of Medical Oncology, Balkan Oncology Hospital, 22030 Edirne, Turkey. Electronic address: irfancicin@trakya.edu.tr.

² Alexander Fleming Institution, Cramer 1180 caba, Buenos Aires CP 1426, Argentina. Electronic address: claudiomartin17@outlook.com.

³ Thoracic Oncology Department, DASA Group, Hospital Nove de Julho, Rua Peixoto Gomide, 545 - 4th floor, Build B, 01409-002 São Paulo, SP, Brazil. Electronic address: carolina.oncologia@yahoo.com.

⁴ Asan Medical Center, 88, Olympic-ro, 43-gil, Songpa-gu, Seoul 05505, South Korea. Electronic address: swkim@amc.seoul.kr.

⁵ Burdenko Main Military Hospital, Radiation Oncology Center, Gospitalnaya pl.3, Moscow 105094, Russia. Electronic address: smolingvkg@gmail.com.

⁶ Takeda Pharmaceuticals International AG, 8 Marina Boulevard, #15-01, Marina Bay Financial Centre, 018981, Singapore. Electronic address: arif.abdillah@takeda.com.

⁷ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Fucheng Road No.52 Haidian District, Beijing 100142, China. Electronic address: dryangxue2010@163.com.

¹ Trakya University, Faculty of Medicine, Department of Medical Oncology, Balkan Oncology Hospital, 22030 Edirne, Turkey. Electronic address: irfancicin@trakya.edu.tr.

² Alexander Fleming Institution, Cramer 1180 caba, Buenos Aires CP 1426, Argentina. Electronic address: claudiomartin17@outlook.com.

³ Thoracic Oncology Department, DASA Group, Hospital Nove de Julho, Rua Peixoto Gomide, 545 - 4th floor, Build B, 01409-002 São Paulo, SP, Brazil. Electronic address: carolina.oncologia@yahoo.com.

⁴ Asan Medical Center, 88, Olympic-ro, 43-gil, Songpa-gu, Seoul 05505, South Korea. Electronic address: swkim@amc.seoul.kr.

⁵ Burdenko Main Military Hospital, Radiation Oncology Center, Gospitalnaya pl.3, Moscow 105094, Russia. Electronic address: smolingvkg@gmail.com.

⁶ Takeda Pharmaceuticals International AG, 8 Marina Boulevard, #15-01, Marina Bay Financial Centre, 018981, Singapore. Electronic address: arif.abdillah@takeda.com.

⁷ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Fucheng Road No.52 Haidian District, Beijing 100142, China. Electronic address: dryangxue2010@163.com.

This article reviews the role of ALK tyrosine kinase inhibitors (TKIs) in the literature and provides expert commentary on local use in Argentina, Brazil, China, Russia, South Korea, and Turkey. We identified 56 articles involving patients with ALK-positive non-small cell lung cancer (NSCLC) and brain metastases (BM) treated with ALK TKIs published between January 2000 and June 2021. In first-line settings, central nervous system response rates in clinical trials with alectinib (86-94%), brigatinib (67-78%), and lorlatinib (42-82%) were generally higher than those reported with crizotinib (16-71%). Median progression-free survival in patients receiving crizotinib (5.6-7.4 months) was lower than alectinib (not reached), brigatinib (24.0 months), and ceritinib (10.7-25.2 months). Across these counties, next-generation TKIs are preferred for patients with progressing BM lesions. Although next-generation ALK TKIs demonstrate significant activity in these patients and following progression on crizotinib, access remains a challenge for personalized therapy.

Conflicts of interest IC has received honoraria for lectures/advisory boards/consultancy from Pfizer, MSD, Roche, Novartis, Ipsen, Eli Lilly, BMS, SERVIER, Abdi Ibrahim, Nobelpharma, AbbVie, Teva, Janssen, Takeda; received funding for research/grants from Pfizer, MSD, Roche, Eli Lilly, BMS, SERVIER, AstraZeneca, AbbVie, Sanofi, Amgen, and Janssen. CM has received honoraria for lectures/advisory boards/consultancy from Pfizer, Takeda, AstraZeneca, Boehringer Ingelheim, BMS. CKH has conducted research for Bristol Myers Squibb (BMS), Merck, Sharp & Dohme (MSD), Roche, Pfizer, Novartis, AstraZeneca, Takeda, and Amgen; and received honoraria for lectures/advisory boards/consultancy from BMS, MSD, Roche, Pfizer, Novartis, AstraZeneca, Takeda, Amgen, Bayer, Sanofi, Janssen, and Eli Lilly. SK has received honoraria for lectures/advisory boards from AstraZeneca, Amgen, Boehringer Ingelheim, Janssen, Novartis, Eli Lilly, Takeda, and Yuhan; received funding for research/grants from AstraZeneca and Boehringer Ingelheim. AS has received honoraria for lectures/advisory boards/consultancy from BMS, Roche, AstraZeneca, Eli Lilly, BIOCAD, and Takeda; received funding for research/grants from BMS, MSD, Roche, AstraZeneca, Amgen, Eli Lilly, Ipsen, and BIOCAD. AA was an employee of Takeda Pharmaceuticals during the time of manuscript preparation and is now an employee of GlaxoSmithKline Pte Limited. XY has received honoraria for lectures/advisory boards/consultancy from BMS, MSD, Roche, Novartis, AstraZeneca, Beigene, HengRui, and XinDa.

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