Taiwan Nationwide Study of First-Line ALK-TKI Therapy in ALK-Positive Lung Adenocarcinoma

Zhe-Rong Zheng; Jia-Jun Wu; Chun-Ju Chiang; Tzu-I Chen; Kun-Chieh Chen; Cheng-Hsiang Chu; Sheng-Yi Lin; Sung-Liang Yu; Wen-Chung Lee; Tsang-Wu Liu; Gee-Chen Chang

doi:10.1007/s11523-024-01104-6

Taiwan Nationwide Study of First-Line ALK-TKI Therapy in ALK-Positive Lung Adenocarcinoma

Target Oncol. 2024 Oct 11. doi: 10.1007/s11523-024-01104-6. Online ahead of print.

Authors

Zhe-Rong Zheng^#^{1

2

3}, Jia-Jun Wu^#^{1

2

3}, Chun-Ju Chiang^{4

5}, Tzu-I Chen^{6

7

8}, Kun-Chieh Chen^{1

2

3}, Cheng-Hsiang Chu^{1

2

3}, Sheng-Yi Lin⁹, Sung-Liang Yu^{10

11}, Wen-Chung Lee^{4

5

12}, Tsang-Wu Liu¹³, Gee-Chen Chang^{14

15

16

17}

Affiliations

¹ Institute of Medicine, Chung Shan Medical University, No. 110, Sect. 1, Jianguo N. Road, Taichung, 402, Taiwan.
² School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
³ Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, No.110, Sect. 1, Jianguo N. Road, Taichung, 402, Taiwan.
⁴ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, No.17, Xu-Zhou Road, Taipei, 100, Taiwan.
⁵ Taiwan Cancer Registry, Taipei, Taiwan.
⁶ School of Medicine, College of Medicine, Xinzhuang Dist., Fu-Jen Catholic University, No. 510, Zhongzheng Rd, New Taipei City, 242062, Taiwan.
⁷ National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
⁸ Department of Healthcare Administration, Asia University, Taichung, Taiwan.
⁹ Department of Anatomy, School of Medicine, College of Medicine, Chung Shan Medical University, No. 110, Sect. 1, Jianguo N. Road, Taichung, 402, Taiwan.
¹⁰ Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, No. 1, Changde St., Taipei, 10048, Taiwan.
¹¹ Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
¹² Institute of Health Data Analytics and Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan.
¹³ National Institute of Cancer Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan, Miaoli County, 35053, Taiwan.
¹⁴ Institute of Medicine, Chung Shan Medical University, No. 110, Sect. 1, Jianguo N. Road, Taichung, 402, Taiwan. geechen@gmail.com.
¹⁵ School of Medicine, Chung Shan Medical University, Taichung, Taiwan. geechen@gmail.com.
¹⁶ Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, No.110, Sect. 1, Jianguo N. Road, Taichung, 402, Taiwan. geechen@gmail.com.
¹⁷ Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan. geechen@gmail.com.

^# Contributed equally.

PMID: 39392550
DOI: 10.1007/s11523-024-01104-6

Abstract

Background: The clinical outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced lung adenocarcinoma vary according to real-world data.

Objective: In this study, we aimed to investigate the treatment discontinuation (TTD) and overall survival (OS) of patients with ALK+ advanced lung adenocarcinoma treated with first-line ALK-TKIs in Taiwan.

Patients and methods: This retrospective study evaluated all advanced lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2020 who had ALK rearrangement and received ALK-TKI treatment, using data from Taiwan's National Health Insurance Research Database (NHIRD). The TKI treatment sequences were classified into first generation (G1: crizotinib), second generation (G2: ceritinib, alectinib, brigatinib), and third generation (G3: lorlatinib).

Results: A total of 587 patients were analyzed, with a median age of 60.0 years, 91 (15.5%) aged ≥ 74 years, 293 (49.9%) female, 397 (67.6%) never smoked, and 534 (91.0%) with stage IV disease. Patients who received next-generation ALK-TKIs during the treatment course had longer median time to ALK-TKI TTD and OS. The TTD of the G1, G1+2, G1+2+3, G2, and G2+3 groups was 7.5 (5.4-11.1), 40.6 (29.4-not calculated (NC)), 50.3 (41.3-NC), 34.3 (29.2-43.0), and 36.3 (22.4-NC) months, respectively (p < 0.001). The median OS of the patients in the G1, G1+2, G1+2+3, G2, and G2+3 groups was 10.6 (7.5-14.6), not reached (NR) (NC-NC), NR (NC-NC), 43.0 (36.3-NC), and NR (30.3-NC) months, respectively (p < 0.001). Compared with treatment with crizotinib alone, the multivariate analysis revealed that treatment with next-generation TKIs was independently associated with longer TTD (G1+2 (hazard ratio (HR), 0.24; 95% CI 0.17-0.33; p < 0.001), G1+2+3 or G1+3 (HR, 0.17; 95% confidence interval (CI), 0.10-0.28; p < 0.001), G2 (HR, 0.26; 95% CI 0.19-0.36; p < 0.001), and G2+3 (HR, 0.25; 95% CI 0.14-0.44; p < 0.001)) and median OS (G12 (HR, 0.24; 95% CI 0.17-0.35; p < 0.001), G1+2+3 or G1+3 (HR, 0.09; 95% CI 0.04-0.21; p < 0.001), G2 (HR, 0.22; 95% CI 0.15-0.31; p < 0.001), and G2+3 (HR, 0.20; 95% CI 0.10-0.42; p < 0.001)).

Conclusions: For patients with ALK+ NSCLC, treatments including next-generation ALK-TKIs were independently associated with longer survival outcomes.

Abstract

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