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表皮生长因子受体(EGFR)酪氨酸激酶抑制剂治疗后疾病进展的EGFR突变型非鳞状细胞肺癌患者的免疫治疗加化疗:一项随机对照试验的荟萃分析

Immunotherapy plus Chemotherapy for Patients with EGFR-Mutated Non-Squamous Cell Lung Cancer for Disease Progression after EGFR Tyrosine-Kinase Inhibitor: A Meta-Analysis of Randomized Controlled Trials.

作者信息

Refae Ahmed A, Abu Shakra Rafat I, Ibrahim Ezzeldin M

机构信息

Oncology Department, King's College London, Jeddah, Saudi Arabia.

Oncology Center of Excellence, International Medical Center, Jeddah, Saudi Arabia.

出版信息

Oncology. 2025;103(5):400-412. doi: 10.1159/000541415. Epub 2024 Sep 16.

Abstract

INTRODUCTION

Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations face poor outcomes after progression on tyrosine kinase inhibitors (TKIs). The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in these patients remains uncertain.

METHODS

We searched for studies published between randomized controlled trials of ICIs in combination therapies in advanced NSCLC patients post-EGFR TKI progression. Data on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were extracted and analyzed.

RESULTS

Six studies with a total of 2,225 patients were analyzed. The pooled hazard ratio (HR) for PFS was 0.60 (95% CI, 0.55-0.65; p < 0.0001), indicating a significant improvement in PFS with ICIs. Subgroup analysis suggested that patients with prior exposure to third-generation TKIs showed a more pronounced benefit (HR = 0.61; 95% CI, 0.49-0.76; p < 0.0001). However, no benefit was found in patients without prior exposure. The efficacy of the experimental interventions was also shown on the pooled estimates of OS (HR = 0.87; 95% CI, 0.77-0.0.99; p value = 0.04) and ORR (OR = 1.91; 95% CI, 1.32-2.76; p < 0.0001).

CONCLUSION

ICIs may significantly benefit PFS among patients with EGFR-mutated NSCLC who have progressed on TKI treatment. Future research should continue stratifying patients based on prior treatment exposure to optimize therapeutic strategies.

摘要

引言

携带表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)患者在酪氨酸激酶抑制剂(TKIs)治疗进展后预后较差。免疫检查点抑制剂(ICIs)联合化疗在这些患者中的疗效仍不确定。

方法

我们检索了EGFR TKI治疗进展后的晚期NSCLC患者中ICIs联合治疗的随机对照试验之间发表的研究。提取并分析了无进展生存期(PFS)、总生存期(OS)和客观缓解率(ORR)的数据。

结果

分析了6项研究,共2225例患者。PFS的合并风险比(HR)为0.60(95%CI,0.55 - 0.65;p < 0.0001),表明ICIs可显著改善PFS。亚组分析表明,先前接受过第三代TKIs治疗的患者获益更显著(HR = 0.61;95%CI,0.49 - 0.76;p < 0.0001)。然而,未接受过先前治疗的患者未发现获益。实验性干预措施在OS(HR = 0.87;95%CI,0.77 - 0.99;p值 = 0.04)和ORR(OR = 1.91;

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d51c/12048105/2949c6d6ce62/ocl-2025-0103-0005-541415_F01.jpg

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