Chemotherapy-Based Combination Regimens for Advanced EGFR-Mutant NSCLC After EGFR-TKI Failure: A Network Meta-Analysis.

IF 14.8 2区 医学 Q1 ONCOLOGY Journal of the National Comprehensive Cancer Network Pub Date : 2025-03-13 DOI:10.6004/jnccn.2024.7092
Lan-Lan Pang, Wei-Tao Zhuang, Zi-Hong Chen, Jun Liao, Meng-Di Li, Li Zhang, Wen-Feng Fang, Ya-Xiong Zhang
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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.

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来源期刊
CiteScore
20.20
自引率
0.00%
发文量
388
审稿时长
4-8 weeks
期刊介绍: JNCCN—Journal of the National Comprehensive Cancer Network is a peer-reviewed medical journal read by over 25,000 oncologists and cancer care professionals nationwide. This indexed publication delivers the latest insights into best clinical practices, oncology health services research, and translational medicine. Notably, JNCCN provides updates on the NCCN Clinical Practice Guidelines in Oncology® (NCCN Guidelines®), review articles elaborating on guideline recommendations, health services research, and case reports that spotlight molecular insights in patient care. Guided by its vision, JNCCN seeks to advance the mission of NCCN by serving as the primary resource for information on NCCN Guidelines®, innovation in translational medicine, and scientific studies related to oncology health services research. This encompasses quality care and value, bioethics, comparative and cost effectiveness, public policy, and interventional research on supportive care and survivorship. JNCCN boasts indexing by prominent databases such as MEDLINE/PubMed, Chemical Abstracts, Embase, EmCare, and Scopus, reinforcing its standing as a reputable source for comprehensive information in the field of oncology.
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