{"title":"晚期表皮生长因子受体突变 NSCLC 一线联合 EGFR-TKI + 化疗与单用 EGFR-TKI：随机 III 期试验荟萃分析。","authors":"Thierry Landre, Jean-Baptiste Assié, Kader Chouahnia, Gaetan Des Guetz, Jean-Bernard Auliac, Christos Chouaïd","doi":"10.1080/14737140.2024.2362889","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor - receptor (<i>EGFR</i>) mutation. Chemotherapy (ChT) given in combination with an EGFR-TKI in this setting is of interest.</p><p><strong>Methods: </strong>We conducted a meta-analysis of phase III randomized trials comparing EGFR-TKI + ChT vs. EGFR-TKI alone as first-line therapy for advanced NSCLC harboring an activating <i>EGFR</i> mutation.</p><p><strong>Results: </strong>Three studies evaluated gefitinib + ChT (NEJ009, GAP-Brain, and Noronha et al.) and another evaluated osimertinib + ChT (FLAURA-2). Those four eligible studies included 1413 patients with non-squamous NSCLCs, 826 (58%) with an exon-19 deletion (ex19del) and 541 (38%) with <i>EGFR</i><sup><i>L858R</i></sup>. The EGFR-TKI + ChT combination was significantly associated with prolonged PFS (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.45-0.59]; <i>p</i> < 0.0001) and OS (HR: 0.69 [0.52-0.93]; <i>p</i> = 0.01). PFS was particularly improved for patients with brain metastases (HR: 0.41[0.33-0.51]; <i>p</i> < 0.00001).</p><p><strong>Conclusions: </strong>For patients with untreated, advanced, <i>EGFR</i>-mutated NSCLCs, the EGFR-TKI + ChT combination, compared to EGFR-TKI alone, was associated with significantly prolonged PFS and OS. However, further studies are needed to identify which patients will benefit the most from the combination.</p><p><strong>Registration: </strong>PROSPERO CRD42024508055.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"First-line concomitant EGFR-TKI + chemotherapy versus EGFR-TKI alone for advanced <i>EGFR</i>-mutated NSCLC: a meta-analysis of randomized phase III trials.\",\"authors\":\"Thierry Landre, Jean-Baptiste Assié, Kader Chouahnia, Gaetan Des Guetz, Jean-Bernard Auliac, Christos Chouaïd\",\"doi\":\"10.1080/14737140.2024.2362889\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor - receptor (<i>EGFR</i>) mutation. Chemotherapy (ChT) given in combination with an EGFR-TKI in this setting is of interest.</p><p><strong>Methods: </strong>We conducted a meta-analysis of phase III randomized trials comparing EGFR-TKI + ChT vs. EGFR-TKI alone as first-line therapy for advanced NSCLC harboring an activating <i>EGFR</i> mutation.</p><p><strong>Results: </strong>Three studies evaluated gefitinib + ChT (NEJ009, GAP-Brain, and Noronha et al.) and another evaluated osimertinib + ChT (FLAURA-2). Those four eligible studies included 1413 patients with non-squamous NSCLCs, 826 (58%) with an exon-19 deletion (ex19del) and 541 (38%) with <i>EGFR</i><sup><i>L858R</i></sup>. The EGFR-TKI + ChT combination was significantly associated with prolonged PFS (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.45-0.59]; <i>p</i> < 0.0001) and OS (HR: 0.69 [0.52-0.93]; <i>p</i> = 0.01). PFS was particularly improved for patients with brain metastases (HR: 0.41[0.33-0.51]; <i>p</i> < 0.00001).</p><p><strong>Conclusions: </strong>For patients with untreated, advanced, <i>EGFR</i>-mutated NSCLCs, the EGFR-TKI + ChT combination, compared to EGFR-TKI alone, was associated with significantly prolonged PFS and OS. However, further studies are needed to identify which patients will benefit the most from the combination.</p><p><strong>Registration: </strong>PROSPERO CRD42024508055.</p>\",\"PeriodicalId\":12099,\"journal\":{\"name\":\"Expert Review of Anticancer Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Review of Anticancer Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14737140.2024.2362889\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Anticancer Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14737140.2024.2362889","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
First-line concomitant EGFR-TKI + chemotherapy versus EGFR-TKI alone for advanced EGFR-mutated NSCLC: a meta-analysis of randomized phase III trials.
Introduction: A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor - receptor (EGFR) mutation. Chemotherapy (ChT) given in combination with an EGFR-TKI in this setting is of interest.
Methods: We conducted a meta-analysis of phase III randomized trials comparing EGFR-TKI + ChT vs. EGFR-TKI alone as first-line therapy for advanced NSCLC harboring an activating EGFR mutation.
Results: Three studies evaluated gefitinib + ChT (NEJ009, GAP-Brain, and Noronha et al.) and another evaluated osimertinib + ChT (FLAURA-2). Those four eligible studies included 1413 patients with non-squamous NSCLCs, 826 (58%) with an exon-19 deletion (ex19del) and 541 (38%) with EGFRL858R. The EGFR-TKI + ChT combination was significantly associated with prolonged PFS (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.45-0.59]; p < 0.0001) and OS (HR: 0.69 [0.52-0.93]; p = 0.01). PFS was particularly improved for patients with brain metastases (HR: 0.41[0.33-0.51]; p < 0.00001).
Conclusions: For patients with untreated, advanced, EGFR-mutated NSCLCs, the EGFR-TKI + ChT combination, compared to EGFR-TKI alone, was associated with significantly prolonged PFS and OS. However, further studies are needed to identify which patients will benefit the most from the combination.
期刊介绍：
Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches.
Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care.
Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections:
Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results
Article Highlights – an executive summary of the author’s most critical points.
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