OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Lazertinib – Lazcluze®

DRUG CLASS

Antineoplastic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Lazertinib	1903008-80-9	C30-H34-N8-O3

ANNOTATED BIBLIOGRAPHY

References updated: 23 March 2025

Abbreviations: EGF, epidermal growth factor; ULN, upper limit of the normal range.

• Zimmerman HJ. Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of tyrosine kinase inhibitors such as lazertinib).
• DeLeve LD. Erlotinib. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 556.

  (Review of hepatotoxicity of cancer chemotherapeutic agents discusses several tyrosine kinase inhibitors including imatinib, gefitinib, erlotinib and crizotinib, but not lazertinib).
• Wellstein A, Giaccone G, Atkins MB, Sausville EA. Pathway-targeted therapies: monoclonal antibodies, protein kinase inhibitors, and various small molecules. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1203-36.

  (Textbook of pharmacology and therapeutics).
• FDA. Multi-Discipline Review. 2024. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2024/219008Orig1s000MultidisciplineR.pdf

  (FDA review of the data on efficacy and safety of lazertinib in support of its approval for first line therapy of NSCLC when given in combination with amivantamab in the US, mentions that liver test abnormalities were frequent in the 421 patients treated, ALT elevations arising in 65% of lazertinib treated subjects which were above 5 times the upper limit of normal (ULN) in 7%, leading to dose interruptions in 6%, but there were no discontinuations for serum enzyme elevations, and no instances of clinically apparent liver injury).
• Spraggs CF, Xu CF, Hunt CM. Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors. Pharmacogenomics 2013; 14: 541-54. [PubMed: 23556451]

  (Review of genetic associations of serum ALT and bilirubin elevations during therapy with tyrosine kinase inhibitors focusing on lapatinib and pazopanib; lazertinib is not discussed).
• Shah RR, Morganroth J, Shah DR. Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Saf 2013; 36: 491-503. [PubMed: 23620168]

  (Review of the hepatotoxicity of 18 tyrosine kinase inhibitors approved for use in cancer in the US as of 2013, before the availability of lazertinib which is not discussed).
• Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, Cicin I, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small-cell lung cancer: Results from LASER301. J Clin Oncol. 2023;41:4208-4217. [PubMed: 37379502]

  (Among 393 patients with advanced NSCLC treated with lazertinib [240 mg daily] without amivantamab vs gefitinib [250 mg daily] as first line therapy [without previous kinase inhibitor treatment], the median progression-free survival was 20.6 vs 9.7 months, and while overall adverse event rates were similar [96% vs 95%], ALT and AST elevations were fewer with lazertinib [15% vs 30% and 11% vs 26%]).
• Passaro A, Wang J, Wang Y, Lee SH, Melosky B, Shih JY, Wang J, et al.; MARIPOSA-2 Investigators. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024;35:77-90. [PubMed: 37879444]

  (Among 657 patients with EGF receptor mutant, advanced NSCLC refractory of osimertinib who were treated with amivantamab and standard chemotherapy with or without lazertinib or placebo, progression-free survival was highest with amivantamab combined with lazertinib [8.3 months] vs amivantamab and chemotherapy [6.3 months] and chemotherapy alone [4.2 months], but so were serious adverse events [57% vs 32% vs 20%], but rates of ALT elevations were similar [21% vs 20% vs 28%] including elevations above 5 times ULN [5% vs 5% vs 4%], and there were no reports of liver injury with jaundice).
• Chul Cho B, Han JY, Hyeong Lee K, Lee YG, Kim DW, Joo Min Y, Kim SW, et al. Lazertinib as a frontline treatment in patients with EGFR-mutated advanced non-small cell lung cancer: long-term follow-up results from LASER201. Lung Cancer. 2024;190:107509. [PubMed: 38432025]

  (Among 43 patients with advanced NSCLC treated with lazertinib [240 mg daily] without amivantamab as first line therapy [without previous kinase inhibitor treatment], the objective response rate was 70% and median progression-free survival 24.6 months, while adverse events occurred 100% and were severe in 37%, ALT elevations arising in 26% that were above 5 times ULN in 5%).
• Leighl NB, Akamatsu H, Lim SM, Cheng Y, Minchom AR, Marmarelis ME, Sanborn RE, et al.; PALOMA-3 Investigators. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory epidermal growth factor receptor-mutated non-small cell lung cancer: primary results from the phase III PALOMA-3 study. J Clin Oncol. 2024;42:3593-3605. [PMC free article: PMC11469630] [PubMed: 38857463]

  (Among 418 patients with refractory, EGF receptor mutated NSCLC treated with lazertinib and either subcutaneous or intravenous amivantamab, the objective response rate was similar while infusion related reactions were fewer with sc dosing [13% vs 66%] and therapy was in general better tolerated, ALT elevations arising in 20% vs 21% and were above 5 times ULN in 1% of both groups).
• Lazertinib (Lazcluze) for non-small cell lung cancer. Med Lett Drugs Ther. 2024;66:e176-e177. [PubMed: 39466312]

  (Concise review of the mechanism of action, clinical efficacy, safety, and costs of lazertinib shortly after its approval as therapy in combination with amivantamab in 2024, mentions the many side effects of combination therapy but does not mention ALT elevations or hepatotoxicity).
• Cho BC, Lu S, Felip E, Spira AI, Girard N, Lee JS, Lee SH, et al.; MARIPOSA Investigators. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. 2024;391(16):1486-1498. [PubMed: 38924756]

  (Among 1074 adults with advanced NSCLC harboring EGF receptor mutations [exon 19 deletion or L858R] treated with lazertinib with or without amivantamab vs osimertinib, progression-free survival was longer with the combination vs osimertinib [23.7 vs 16.6 months], while serious adverse events rates were higher [49% vs 33%] as were dose reductions [59% vs 5%], discontinuations [35% vs 14%] and ALT elevations [36% vs 13%], which were above 5 times ULN in 5% vs 2%] but there were no discontinuations for liver injury].