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

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

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

Zhe-Rong Zheng et al. Target Oncol. 2024 Nov.

. 2024 Nov;19(6):941-955.

doi: 10.1007/s11523-024-01104-6. Epub 2024 Oct 11.

Authors

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.

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Conflict of interest statement

Declarations Funding This study was funded by Pfizer (tracking no. 75046155), the Ministry of Health and Welfare (MOHW112-TDU-B-222-124019), and Formatting the Risk Prediction Models for Never-Smoking Lung Cancer (FORMOSA). Conflict of interest 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, and Gee-Chen Chang declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Ethics approval The study was approved by the Institutional Review Board (IRB) of CSMUH, Taiwan (IRB no. CS1-22160). Consent to participate Not applicable. Consent for publication All authors reviewed the manuscript and approved the version for publication. Availability of data and material The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Code availability Not applicable. Author contributions Zhe-Rong Zheng, Jia-Jun Wu, Chun-Ju Chiang, and Gee-Chen Chang contributed to the study conception and design. Material preparation and data collection were performed by Jia-Jun Wu and Chun-Ju Chiang. The analysis of the data was done by Jia-Jun Wu, Chun-Ju Chiang, Tzu-I Chen, Kun-Chieh Chen, and Gee-Chen Chang. The writing of the original draft was performed by 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, and Gee-Chen Chang. Jia-Jun Wu and Gee-Chen Chang revised the manuscript critically for important intellectual content.

References

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

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

Authors

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Conflict of interest statement

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