Simona Stefania Juncu Anca Victorita Trifan Horia Minea Raluca-Ioana Avram Camelia Cojocariu Ana-Maria Singeap


Novel oncological therapies substantially improved the prognosis of cancer patients. Immunotherapies (immune checkpoint inhibitors) and targeted therapies (tyrosine kinase inhibitors) represent innovative strategies, which have revolutionized cancer patients approaches. However, the new treatments may bring additional adverse effects, therefore right selection, close monitoring, and appropriate clinical decisions in the event of a complication are of upmost importance in these patients' management. We present an elderly male patient undergoing treatment with alectinib - anaplastic lymphoma kinase (ALK) inhibitor for metastatic non-small cell lung cancer, who was diagnosed with acute liver failure by drug-induced liver injury, five months after the start of the therapy. After the other possible causes of hepatocellular injury were excluded, the drug was discontinued. Using corticotherapy and supportive measures, the evolution of the patient was favorable. Up to this moment, data showed that alectinib was less associated with liver function abnormalities compared to other ALK inhibitors, however most commonly of mild or moderate grade of severity, especially in the first two months of treatment. The case we report presented acute onset liver failure, with a relatively late occurrence during alectinib therapy. Timely recognition may improve patients prognosis, and monitoring must be carried out rigorously. Awareness and effective interdisciplinary communication among medical specialties play a pivotal role in the comprehensive care of cancer patients.



targeted therapy, ALK inhibitors, alectinib, non-small cell lung cancer, drug-induced liver injury, acute liver failure

1. Charmsaz S, Collins DM, Perry AS, Prencipe M. Novel Strategies for Cancer Treatment: Highlights from the 55th IACR Annual Conference. Cancers (Basel). 2019;11(8):1125. doi: 10.3390/cancers11081125. PMID: 31394729; PMCID: PMC6721818.
2. Bondhopadhyay B, Sisodiya S, Chikara A, Khan A, Tanwar P, Afroze D, Singh N, Agrawal U, Mehrotra R, Hussain S. Cancer immunotherapy: a promising dawn in cancer research. Am J Blood Res. 2020;10(6):375-385. PMID: 33489447; PMCID: PMC7811907.
3. Min HY, Lee HY. Molecular targeted therapy for anticancer treatment. Exp Mol Med. 2022;54(10):1670-1694. doi: 10.1038/s12276-022-00864-3. PMID: 36224343; PMCID: PMC9636149.
4. Malnick SDH, Abdullah A, Neuman MG. Checkpoint Inhibitors and Hepatotoxicity. Biomedicines. 2021;9(2):101. doi: 10.3390/biomedicines9020101. PMID: 33494227; PMCID: PMC7909829.
5. Zhou Z, Li M. Targeted therapies for cancer. BMC Med. 2022;20(1):90. doi: 10.1186/s12916-022-02287-3. PMID: 35272686; PMCID: PMC8915534.
6. Yuan L, Kaplowitz N. Mechanisms of drug-induced liver injury. Clin Liver Dis. 2013;17(4):507-18, vii. doi: 10.1016/j.cld.2013.07.002. PMID: 24099014; PMCID: PMC3793205.
7. Katarey D, Verma S. Drug-induced liver injury. Clin Med (Lond). 2016;16(Suppl 6):s104-s109. doi: 10.7861/clinmedicine.16-6-s104. PMID: 27956449; PMCID: PMC6329561.
8. Hosack T, Damry D, Biswas S. Drug-induced liver injury: a comprehensive review. Therap Adv Gastroenterol. 2023;16:17562848231163410. doi: 10.1177/17562848231163410. PMID: 36968618; PMCID: PMC10031606.
9. Fisher K, Vuppalanchi R, Saxena R. Drug-Induced Liver Injury. Arch Pathol Lab Med. 2015;139(7):876-887. doi: 10.5858/arpa.2014-0214-RA. PMID: 26125428.
10. Teschke R. Treatment of Drug-Induced Liver Injury. Biomedicines. 2022;11(1):15. doi: 10.3390/biomedicines11010015. PMID: 36672522; PMCID: PMC9855719.
11. Clinton JW, Kiparizoska S, Aggarwal S, et al. Drug-Induced Liver Injury: Highlights and Controversies in the Recent Literature. Drug Saf. 2021;44(11):1125-1149. doi: 10.1007/s40264-021-01109-4. PMID: 34533782; PMCID: PMC8447115.
12. Chevallier M, Borgeaud M, Addeo A, Friedlaender A. Oncogenic driver mutations in non-small cell lung cancer: Past, present and future. World J Clin Oncol. 2021;12(4):217-237. doi: 10.5306/wjco.v12.i4.217. PMID: 33959476; PMCID: PMC8085514.
13. Huang H. Anaplastic Lymphoma Kinase (ALK) Receptor Tyrosine Kinase: A Catalytic Receptor with Many Faces. Int J Mol Sci. 2018;19(11):3448. doi: 10.3390/ijms19113448. PMID: 30400214; PMCID: PMC6274813.
14. Chia PL, Mitchell P, Dobrovic A, John T. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clin Epidemiol. 2014;6:423-432. doi: 10.2147/CLEP.S69718. PMID: 25429239; PMCID: PMC4242069.
15. Mori M, Hayashi H, Fukuda M, et al. Clinical and computed tomography characteristics of non-small cell lung cancer with ALK gene rearrangement: Comparison with EGFR mutation and ALK/EGFR-negative lung cancer. Thorac Cancer. 2019;10(4):872-879. doi: 10.1111/1759-7714.13017. PMID: 30811109; PMCID: PMC6449252.
16. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167-2177. doi: 10.1056/NEJMoa1408440. Erratum in: N Engl J Med. 2015;373(16):1582. PMID: 25470694.
17. Gadgeel S, Peters S, Mok T, et al. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALKþ) non-small cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018; 29:2214-2222. PMID: 29455675; PMCID: PMC5817728. doi: 10.1186/s12943-018-0810-4.
18. Zhou C: Primary results of ALESIA: A randomised, phase III, openlabel study of alectinib vs crizotinib in Asian patients with treatment naïve ALK+advanced NSCLC [ available at 11.01.2023]
19. Liu B, Yuan M, Sun Y, et al. Incidence and risk of hepatic toxicities associated with anaplastic lymphoma kinase inhibitors in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2017;9(10):9480-9488. doi: 10.18632/oncotarget.23840. PMID: 29507704; PMCID: PMC5823621.
20. Zhu Q, Hu H, Weng DS, et al. Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC. BMC Cancer. 2017;17(1):412. doi: 10.1186/s12885-017-3405-3. PMID: 28606126; PMCID: PMC5469041.
21. Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017;390(10089):29-39. doi: 10.1016/S0140-6736(17)30565-2. PMID: 28501140.
22. Yao ZH, Liao WY, Ho CC, et al. Incidence of hepatitis B reactivation during epidermal growth factor receptor tyrosine kinase inhibitor treatment in non-small-cell lung cancer patients. Eur J Cancer. 2019;117:107-115. doi: 10.1016/j.ejca.2019.05.032. PMID: 31279301.
23. Viganò M, La Milia M, Grassini MV, et al. Hepatotoxicity of Small Molecule Protein Kinase Inhibitors for Cancer. Cancers (Basel). 2023;15(6):1766. doi: 10.3390/cancers15061766. PMID: 36980652; PMCID: PMC10046041.
24. Zhou F, Yang Y, Zhang L, et al. Expert consensus of management of adverse drug reactions with anaplastic lymphoma kinase tyrosine kinase inhibitors. ESMO Open. 2023;8(3):101560. doi: 10.1016/j.esmoop.2023.101560. PMID: 37230029; PMCID: PMC10225873.
How to Cite
Juncu, S. S., Trifan, A. V., Minea, H., Avram, R.-I., Cojocariu, C., & Singeap, A.-M. (2023). From spotlight to shadow: ALK inhibitor-induced acute liver failure in a patient with non-small cell lung cancer. Archive of Clinical Cases, 10(4), Arch Clin Cases. 2023;10(4):160-163.
Case Reports

How to Cite

Juncu, S. S., Trifan, A. V., Minea, H., Avram, R.-I., Cojocariu, C., & Singeap, A.-M. (2023). From spotlight to shadow: ALK inhibitor-induced acute liver failure in a patient with non-small cell lung cancer. Archive of Clinical Cases, 10(4), Arch Clin Cases. 2023;10(4):160-163.