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Lazertinib: on the Way to Its Throne

홍민희|조병철|이지윤
연세대학교의과대학 (Yonsei University College of Medicine)|2022.09|Yonsei Medical Journal|제63권 제9호|pp. 799-805|DOI 10.3349/ymj.2022.63.9.799

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참고문헌

키워드

targeted therapynon-small cell lung cancerLazertinibepidermal growth factor receptor
주제분류의학일반

초록

Lazertinib is an oral, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) thatforms an irreversible covalent bond to the Cys797 residue in the ATP-binding site of the EGFR kinase domain and exhibits a highselectivity for sensitizing and T790M EGFR mutations. In January 2021, it was first approved for the treatment of advanced ormetastatic non-small cell lung cancer (NSCLC) patients with EGFR T790M who had previously received EGFR TKI therapy basedon LASER201, a phase I/II trial. At a recommended dose of 240 mg, lazertinib achieved an encouraging anti-tumor activity in bothextra- and intracranial lesions. With a high half-maximal inhibitory concentration for EGFR wildtype tumors, it is anticipated topose a lower risk of skin and cardiac adverse events compared to osimertinib. Lazertinib is currently being investigated as a mono-therapy in first-line treatment and in combination with amivantamab under various settings. In this review, we systematically sum-marize the preclinical and clinical data of lazertinib and discuss future perspectives on the treatment of EGFR-mutant NSCLC.

Abstract

Lazertinib is an oral, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) thatforms an irreversible covalent bond to the Cys797 residue in the ATP-binding site of the EGFR kinase domain and exhibits a highselectivity for sensitizing and T790M EGFR mutations. In January 2021, it was first approved for the treatment of advanced ormetastatic non-small cell lung cancer (NSCLC) patients with EGFR T790M who had previously received EGFR TKI therapy basedon LASER201, a phase I/II trial. At a recommended dose of 240 mg, lazertinib achieved an encouraging anti-tumor activity in bothextra- and intracranial lesions. With a high half-maximal inhibitory concentration for EGFR wildtype tumors, it is anticipated topose a lower risk of skin and cardiac adverse events compared to osimertinib. Lazertinib is currently being investigated as a mono-therapy in first-line treatment and in combination with amivantamab under various settings. In this review, we systematically sum-marize the preclinical and clinical data of lazertinib and discuss future perspectives on the treatment of EGFR-mutant NSCLC.

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EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation구보미, 박근칠, 박세훈, 선종무, 안명주, 안진석, 이세훈, 정현애대한암학회 · Cancer Research and Treatment2020 · 제52권 제4호Lazertinib versus Gefitinib as First-Line Treatment for EGFR-Mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset강진형, 고윤호, 김동완, 김상위, 김주항, 김진수, 민영주, 박건욱, 신상원, 심병용, 안명주, 왕장영, 이경원, 이경희, 이기형, 이성숙, 이영주, 이윤규, 이종석, 전상훈, 조병철, 조은경, 최석영, 최진혁대한암학회 · Cancer Research and Treatment2024 · 제56권 제1호A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR–Tyrosine Kinase Inhibitors김상위, 김혜영, 남병호, 민영주, 이건국, 이기형, 이수현, 이영주, 이진수, 정진아, 조은경, 한지연, 한혜선대한암학회 · Cancer Research and Treatment2017 · 제49권 제1호Treatment of Non-small Cell Lung Carcinoma after Failure of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor김영철, 이계영, 이재철, 장승훈대한암학회 · Cancer Research and Treatment2013 · 제45권 제2호Epidermal Growth Factor Receptor Mutation Status in the Treatment of Non-small Cell Lung Cancer: Lessons Learned이대호, Mauro Orlando, Rebecca Cheng, Vichien Srimuninnimit, Xin Wang대한암학회 · Cancer Research and Treatment2015 · 제47권 제4호Osimertinib in Patients with T790M-Positive Advanced Non-small Cell Lung Cancer: Korean Subgroup Analysis from Phase II Studies강진형, 김동완, 김상위, 안명주, 이종석, 조병철, 한지연, James Chih-Hsin Yang, Tetsuya Mitsudomi대한암학회 · Cancer Research and Treatment2020 · 제52권 제1호

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