The efficacy of immunotherapy in non-small cell lung cancer with KRAS mutation: a systematic review and meta-analysis.

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-11-01 DOI:10.1186/s12935-024-03498-9

Rui Zhao, Yang Shu, Wei Xu, Fengxian Jiang, Pancen Ran, Liying Pan, Jingliang Wang, Weihao Wang, Jing Zhao, Yahui Wang, Guobin Fu

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Abstract

Purpose: The KRAS mutation is highly prevalent in NSCLC and is associated with poor efficacy of immunotherapy. Nevertheless, the impact of KRAS mutation, mutation subtypes, and co-mutations on the effectiveness of immunotherapy remains uncertain. This study aimed to assess the influence of the KRAS mutation on the effectiveness of immunotherapy in NSCLC, specifically examining different subtypes of KRAS mutations and co-mutations.

Methods: We performed an extensive search of multiple databases, covering the period from January 1, 2000, to December 5, 2023. A total of 24 articles met our inclusion criteria and were included in this study. A comparative analysis assessed the influence of different subgroups, including KRAS mutation, KRAS wild-type, KRAS G12C mutation, KRAS G12D mutation, and KRAS with co-mutations in NSCLC with immunotherapy. The study outcomes include HR, with corresponding 95% CI and P-values for OS and PFS using Review Manager 5.4 software for the meta-analysis.

Result: The KRAS mutation appears to have a more beneficial impact on OS (HR 0.54 [95% CI: 0.41-0.71]; P < 0.00001) and PFS (HR 0.63 [95% CI: 0.53-0.76]; P < 0.00001) in NSCLC patients receiving immunotherapy compared to those without immunotherapy. The presence of KRASG12C mutation has been found to have a positive impact on PFS (HR 0.39 [95% CI: 0.25-0.62]; P < 0.0001) in NSCLC patients who undergo immunotherapy, compared to those who did not receive immunotherapy. KRAS non-G12D mutation is considerably associated with longer OS (HR 1.52 [95% CI: 1.10-2.10]; P = 0.01). The clinical benefit in OS between patients without STK11 co-mutation and those who have KRAS mutation with STK11 is significant (HR 1.46 [95% CI: 1.10-1.93]; P = 0.008). Comparing the impact of OS patients without KEAP1/NFE2L2 mutation to those with KRAS and KEAP1/NFE2L2 co-mutations showed a significant impact (HR 1.89 [95% CI: 1.33-2.68]; P = 0.0004).

Conclusion: The KRAS mutation and KRAS G12C mutation confer benefits that impact OS and PFS in NSCLC patients treated with immunotherapy. However, the KRAS G12D mutation negatively impacts OS compared to the KRAS non-G12D mutation. Furthermore, KRAS co-mutations involving STK11 and KEAP1/NFE2L2 are associated with a negative impact on the efficacy of immunotherapy in NSCLC patients.

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免疫疗法对 KRAS 突变非小细胞肺癌的疗效：系统综述与荟萃分析。

目的：KRAS突变在NSCLC中非常普遍，与免疫疗法疗效不佳有关。然而，KRAS突变、突变亚型和共突变对免疫疗法疗效的影响仍不确定。本研究旨在评估KRAS突变对NSCLC免疫治疗效果的影响，特别是研究KRAS突变的不同亚型和共突变：我们对 2000 年 1 月 1 日至 2023 年 12 月 5 日期间的多个数据库进行了广泛检索。共有 24 篇文章符合我们的纳入标准并被纳入本研究。比较分析评估了不同亚组（包括KRAS突变、KRAS野生型、KRAS G12C突变、KRAS G12D突变和KRAS共突变）对接受免疫疗法的NSCLC的影响。研究结果包括HR，以及OS和PFS的相应95% CI和P值，使用Review Manager 5.4软件进行荟萃分析：结果：KRAS突变似乎对OS有更有利的影响（HR为0.54 [95% CI：0.41-0.71]；P结论：KRAS突变和KRAS突变对OS和PFS有更有利的影响：KRAS突变和KRAS G12C突变对接受免疫疗法治疗的NSCLC患者的OS和PFS有益处。然而，与 KRAS 非 G12D 突变相比，KRAS G12D 突变会对 OS 产生负面影响。此外，涉及 STK11 和 KEAP1/NFE2L2 的 KRAS 共突变也会对 NSCLC 患者接受免疫疗法的疗效产生负面影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.