Investigating osimertinib plus chemotherapy in EGFR-mutated advanced non-small cell lung cancer

奥西默替尼 医学 肺癌 肿瘤科 耐受性 化疗 内科学 埃罗替尼 临床试验 癌症 表皮生长因子受体 不利影响
作者
Alessia Spagnuolo,Cesare Gridelli
出处
期刊:Expert Opinion on Pharmacotherapy [Taylor & Francis]
卷期号:: 1-11
标识
DOI:10.1080/14656566.2025.2464903
摘要

Worldwide, 15-40% of advanced-stage non-small cell lung cancers (NSCLCs) have an activating EGFR mutation, treatable with tyrosine-kinase inhibitors (TKIs) such as osimertinib, recommended as front-line therapy. Despite the efficacy of first-line osimertinib, most patients will experience disease progression. Therefore, combining it with chemotherapy has become an area of interest. Osimertinib is a third-generation EGFR-TKI that has extended survival in NSCLC patients with EGFR mutation. However, resistance eventually leads to treatment failure. This has driven the advancement of strategies to overcome resistance to osimertinib. In this setting, the FLAURA2 trial yielded positive results by combining osimertinib with chemotherapy. Additionally, a range of other approaches, including the use of bispecific antibodies and antibody-drug conjugates alongside third-generation EGFR-TKIs or chemotherapy, support the development of novel therapeutic combinations, some of which have already been approved for EGFR-mutated advanced NSCLC. Next to osimertinib monotherapy, expanded upfront treatment options for patients with EGFR-mutated advanced NSCLC require patient selection considering disease extent, toxicity and tolerability, dosing schedule and what the patient can expect through shared decision-making. Further studies are needed to identify the patients who will benefit the most from combination therapies and to sequence the new drugs into the treatment algorithm.
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