Lan-Lan Pang, Wei-Tao Zhuang, Zi-Hong Chen, Jun Liao, Meng-Di Li, Li Zhang, Wen-Feng Fang, Ya-Xiong Zhang
{"title":"Chemotherapy-Based Combination Regimens for Advanced EGFR-Mutant NSCLC After EGFR-TKI Failure: A Network Meta-Analysis.","authors":"Lan-Lan Pang, Wei-Tao Zhuang, Zi-Hong Chen, Jun Liao, Meng-Di Li, Li Zhang, Wen-Feng Fang, Ya-Xiong Zhang","doi":"10.6004/jnccn.2024.7092","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Traditional chemotherapy provides restricted benefits for advanced EGFR-mutant non-small cell lung cancer (NSCLC) after failure of EGFR-tyrosine kinase inhibitors (EGFR-TKIs), necessitating the combined treatment. However, it remains controversial which is the optimal regimen.</p><p><strong>Methods: </strong>Eligible randomized controlled trials (RCTs) comparing various platinum-based chemotherapy (Chemo) regimens in patients with EGFR-mutated NSCLC who experienced disease progression on EGFR-TKIs were included. A Bayesian random-effects network meta-analysis was performed. Progression-free survival (PFS) was analyzed using the logarithm of hazard ratio (HR) and its standard error, whereas objective response rate (ORR) and treatment-related adverse events (TRAEs) were analyzed using odds ratio (OR) and 95% confidence intervals.</p><p><strong>Results: </strong>A total of 9 RCTs involving 2,534 patients with EGFR-TKI resistance, published between 2022 and 2024, were included in the meta-analysis. The analyzed regimens were summarized into 5 arms: platinum-based doublet chemotherapy (\"Chemo\"); immunotherapy + chemotherapy (\"Chemo_IO\"); bevacizumab + chemotherapy (\"Chemo_Bev\"), immunotherapy combined with bevacizumab (or bispecific antibody against PD-1/PD-L1 and VEGF) + chemotherapy (\"Chemo_anti-PD-1/PD-L1_anti-VEGF\"), and amivantamab + chemotherapy (\"Chemo_Ami\"). Compared with \"Chemo,\" both \"Chemo_Ami\" and \"Chemo_anti-PD-1/PD-L1_anti-VEGF\" significantly prolonged PFS (HR, 0.48 [95% CI, 0.32-0.71] and HR, 0.51 [95% CI, 0.41-0.62], respectively) and improved ORR (OR, 3.13 [95% CI, 1.64-5.96] and OR, 2.17 [95% CI, 1.51-3.11], respectively). \"Chemo_Bev\" also significantly reduced the risk of progression (HR, 0.66 [95% CI, 0.45-0.98]). In contrast, \"Chemo_IO\" failed to improve ORR (OR, 1.25 [95% CI, 0.89-1.81]) and provided a modest PFS benefit (HR, 0.78 [95% CI, 0.64-0.95) compared with \"Chemo.\" Furthermore, compared with \"Chemo_IO,\" both \"Chemo_Ami\" and \"Chemo_anti-PD-1/PD-L1_anti-VEGF\" significantly prolonged PFS (HR, 0.62 [95% CI, 0.39-0.95] and HR, 0.65 [95% CI, 0.52-0.81], respectively) and improved ORR (OR, 2.51 [95% CI, 1.17-5.14] and OR, 1.73 [95% CI, 1.13-2.60], respectively). No statistically significant difference in PFS was observed among \"Chemo_Ami,\" \"Chemo_anti-PD-1/PD-L1_anti-VEGF,\" and \"Chemo_Bev.\" Additionally, \"Chemo_Ami\" was associated with a significantly higher incidence of grade 3-5 TRAEs (OR, 3.71 [95% CI, 1.08-12.7]) compared with \"Chemo,\" whereas no significant differences in TRAEs were observed among the other regimens.</p><p><strong>Conclusions: </strong>Antiangiogenic agents may create a therapeutic window for immunotherapy in advanced NSCLC after progression on prior EGFR-TKI treatment. Based on their superior efficacy, \"Chemo_anti-PD-1/PD-L1_anti-VEGF\" and \"Chemo_Ami\" are recommended as preferred treatment options for patients who experienced disease progression on EGFR-TKIs. Our study highlights and updated therapeutic approach for advanced EGFR-mutant NSCLC.</p>","PeriodicalId":17483,"journal":{"name":"Journal of the National Comprehensive Cancer Network","volume":" ","pages":"1-8"},"PeriodicalIF":14.8000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the National Comprehensive Cancer Network","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.6004/jnccn.2024.7092","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Traditional chemotherapy provides restricted benefits for advanced EGFR-mutant non-small cell lung cancer (NSCLC) after failure of EGFR-tyrosine kinase inhibitors (EGFR-TKIs), necessitating the combined treatment. However, it remains controversial which is the optimal regimen.
Methods: Eligible randomized controlled trials (RCTs) comparing various platinum-based chemotherapy (Chemo) regimens in patients with EGFR-mutated NSCLC who experienced disease progression on EGFR-TKIs were included. A Bayesian random-effects network meta-analysis was performed. Progression-free survival (PFS) was analyzed using the logarithm of hazard ratio (HR) and its standard error, whereas objective response rate (ORR) and treatment-related adverse events (TRAEs) were analyzed using odds ratio (OR) and 95% confidence intervals.
Results: A total of 9 RCTs involving 2,534 patients with EGFR-TKI resistance, published between 2022 and 2024, were included in the meta-analysis. The analyzed regimens were summarized into 5 arms: platinum-based doublet chemotherapy ("Chemo"); immunotherapy + chemotherapy ("Chemo_IO"); bevacizumab + chemotherapy ("Chemo_Bev"), immunotherapy combined with bevacizumab (or bispecific antibody against PD-1/PD-L1 and VEGF) + chemotherapy ("Chemo_anti-PD-1/PD-L1_anti-VEGF"), and amivantamab + chemotherapy ("Chemo_Ami"). Compared with "Chemo," both "Chemo_Ami" and "Chemo_anti-PD-1/PD-L1_anti-VEGF" significantly prolonged PFS (HR, 0.48 [95% CI, 0.32-0.71] and HR, 0.51 [95% CI, 0.41-0.62], respectively) and improved ORR (OR, 3.13 [95% CI, 1.64-5.96] and OR, 2.17 [95% CI, 1.51-3.11], respectively). "Chemo_Bev" also significantly reduced the risk of progression (HR, 0.66 [95% CI, 0.45-0.98]). In contrast, "Chemo_IO" failed to improve ORR (OR, 1.25 [95% CI, 0.89-1.81]) and provided a modest PFS benefit (HR, 0.78 [95% CI, 0.64-0.95) compared with "Chemo." Furthermore, compared with "Chemo_IO," both "Chemo_Ami" and "Chemo_anti-PD-1/PD-L1_anti-VEGF" significantly prolonged PFS (HR, 0.62 [95% CI, 0.39-0.95] and HR, 0.65 [95% CI, 0.52-0.81], respectively) and improved ORR (OR, 2.51 [95% CI, 1.17-5.14] and OR, 1.73 [95% CI, 1.13-2.60], respectively). No statistically significant difference in PFS was observed among "Chemo_Ami," "Chemo_anti-PD-1/PD-L1_anti-VEGF," and "Chemo_Bev." Additionally, "Chemo_Ami" was associated with a significantly higher incidence of grade 3-5 TRAEs (OR, 3.71 [95% CI, 1.08-12.7]) compared with "Chemo," whereas no significant differences in TRAEs were observed among the other regimens.
Conclusions: Antiangiogenic agents may create a therapeutic window for immunotherapy in advanced NSCLC after progression on prior EGFR-TKI treatment. Based on their superior efficacy, "Chemo_anti-PD-1/PD-L1_anti-VEGF" and "Chemo_Ami" are recommended as preferred treatment options for patients who experienced disease progression on EGFR-TKIs. Our study highlights and updated therapeutic approach for advanced EGFR-mutant NSCLC.
期刊介绍:
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