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      Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review)

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          Abstract

          The most common oncogenic driver in non-small cell lung cancer (NSCLC) is epidermal growth factor receptor (EGFR) gene mutations, which are more common in Asian (30–50%) than in Caucasian (10–15%) populations. Exon 19 deletion (ex19del) and exon 21 L858R (ex21 L858R) mutations account for ~45 and 40% of all EGFR mutations, respectively. Moreover, EGFR-tyrosine kinase inhibitors (TKIs) may be more effective and improve the quality of life of patients with NSCLC more than chemotherapy regimens. By contrast, patients with the ex21 L858R mutation may have a lower sensitivity and duration of response to EGFR-TKIs as well as a shorter survival compared with those with the ex19del mutation. However, current guidelines classify ex21 L858R and ex19del as the same condition and recommend the same treatment strategy for both. Aiming for precision medicine, the present review introduces and compares different EGFR-TKIs for the ex21 L858R mutation to assess more personalized treatment options for the population with this mutation.

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          Most cited references84

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer

            Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).
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              Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC

              Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                March 2025
                20 December 2024
                20 December 2024
                : 29
                : 3
                : 109
                Affiliations
                [1 ]Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
                [2 ]Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101125, P.R. China
                Author notes
                Correspondence to: Professor Jun-Ling Li or Professor Pu-Yuan Xing, Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 South Lane, Panjiayuan, Beijing 100021, P.R. China, E-mail: lijunlingcicams.ac.cn xingpuyuan@ 123456cicams.ac.cn
                Article
                OL-29-3-14855
                10.3892/ol.2024.14855
                11704875
                ece828ab-ab6d-46b4-81e6-e68494e3698c
                Copyright: © 2025 Liu et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 16 July 2024
                : 01 November 2024
                Funding
                Funded by: Pfizer China
                This report was supported by funding from Pfizer China.
                Categories
                Review

                Oncology & Radiotherapy
                egfr,ex19del,ex21 l858r,nsclc,egfr-tkis
                Oncology & Radiotherapy
                egfr, ex19del, ex21 l858r, nsclc, egfr-tkis

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