Perspective on the Cardiotoxicity of Third-Generation Targeted EGFRs in the Treatment of NSCLC

Ewer, Michael S.; Ewer, Steven M.

doi:10.1016/j.jtocrr.2021.100233

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Osimertinib–a Friend or Foe?1

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2022

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“…Considering that lazertinib demonstrated comparable anti-tumor efficacy to osimertinib, it may be considered a relatively safer option in terms of cardiotoxicity. 47 …”

Section: Osimertinib–a Friend or Foe?mentioning

confidence: 99%

Lazertinib: on the Way to Its Throne

2022

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

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“…Considering that lazertinib demonstrated comparable anti-tumor efficacy to osimertinib, it may be considered a relatively safer option in terms of cardiotoxicity. 47 …”

Section: Osimertinib–a Friend or Foe?mentioning

confidence: 99%