Treating Non-Small-Cell Lung Cancer with Limertinib, a 3rd Generation EGFR Inhibitor
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on August 22nd, 2025
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Mutation to the epidermal growth factor receptor (EGFR) significantly increases the risk of non-small-cell lung cancer (NSCLC). As a result, inhibiting the EGFR signaling pathway becomes an ideal therapeutic target. EGFR tyrosine kinase inhibitors have been shown to be effective at managing NSCLC, but resistance has been shown to be an obstacle. With funding from Jiangsu Aosaikang Pharmaceutical, a study was conducted to investigate the usage of limertinib to treat non-small-cell lung cancer.
The phase 3 clinical study was conducted in China, and it included 337 participants who had been diagnosed with localized advanced or metastatic non-small-cell lung cancer. 95% of the cohort have stage 4 disease. Genetic analysis was performed on the patients to include those who had mutated EGFR. 67% of them having an exon 19 deletion, and the remaining having a leucine-to-arginine mutation on the 858th amino acid on exon 12.
The patients were randomly assigned to be treated with either the new 3rd-generation limertinib or the standard 1st-generation geftinib. Both medications were taken orally with the dose of 80 mg twice daily for limertinib and 250 mg once daily for geftinib. Both medications work by blocking the phosphorylation reaction performed by the tyrosine kinase on the EGFR for signal transduction. However, limertinib can effectively target EGFR with a T790M mutation, which had been an obstacle for earlier generation agents.
The researchers found that the 3rd-generation EGFR tyrosine kinase inhibitor, limertinib, was more effective than geftinib at increasing survival and delaying disease progression. Further subgroup analyses found that this difference in clinical effect is true for patients with different forms of EGFR mutation and metastasis site. Patients treated with limertinib reported a higher frequency of diarrhea, anemia; whereas, geftinib is associated with a higher risk of elevated liver enzyme. Given these promising results, future studies should compare the efficacy between limertinib with other 3rd generation agents; for example, osimertinib can be an ideal candidate due to its widespread use.
The phase 3 clinical study was conducted in China, and it included 337 participants who had been diagnosed with localized advanced or metastatic non-small-cell lung cancer. 95% of the cohort have stage 4 disease. Genetic analysis was performed on the patients to include those who had mutated EGFR. 67% of them having an exon 19 deletion, and the remaining having a leucine-to-arginine mutation on the 858th amino acid on exon 12.
The patients were randomly assigned to be treated with either the new 3rd-generation limertinib or the standard 1st-generation geftinib. Both medications were taken orally with the dose of 80 mg twice daily for limertinib and 250 mg once daily for geftinib. Both medications work by blocking the phosphorylation reaction performed by the tyrosine kinase on the EGFR for signal transduction. However, limertinib can effectively target EGFR with a T790M mutation, which had been an obstacle for earlier generation agents.
The researchers found that the 3rd-generation EGFR tyrosine kinase inhibitor, limertinib, was more effective than geftinib at increasing survival and delaying disease progression. Further subgroup analyses found that this difference in clinical effect is true for patients with different forms of EGFR mutation and metastasis site. Patients treated with limertinib reported a higher frequency of diarrhea, anemia; whereas, geftinib is associated with a higher risk of elevated liver enzyme. Given these promising results, future studies should compare the efficacy between limertinib with other 3rd generation agents; for example, osimertinib can be an ideal candidate due to its widespread use.