Efficacy of first-line immune checkpoint inhibitor and anti-angiogenic agent combination therapy for Kirsten rat sarcoma viral antigen-mutant advanced non-small-cell lung cancer: a systematic review and network meta-analysis.
Akinari Tsukada, Chie Morita, Yosuke Shimizu, Yukari Uemura, Go Naka, Jin Takasaki, Hiroshi Nokihara, Shinyu Izumi, Masayuki Hojo
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引用次数: 0
Abstract
Background: Recent advancements in advanced non-small-cell lung cancer (NSCLC) treatment have significantly improved primary therapy outcomes owing to the emergence of various molecular targeted therapies and immune checkpoint inhibitors (ICIs). However, for Kirsten rat sarcoma viral antigen (KRAS) mutations, molecular targeted drugs, such as sotorasib, are not applicable as first-line treatments, and the optimal primary treatment remains unclear. Therefore, we aimed to investigate the efficacy of ICI combination therapy as first-line treatment for KRAS-mutant NSCLC.
Methods: We conducted a systematic search for phase 3 randomized controlled trials (RCTs) that presented data on KRAS mutation status in advanced NSCLC. The primary endpoints were progression-free survival (PFS) and overall survival (OS). A random-effects network meta-analysis was conducted to perform direct and indirect comparisons among treatment groups.
Results: Six RCTs were eligible for inclusion. In the network meta-analysis for KRAS-mutant NSCLC, Chemo + bevacizumab (Bev) + ICI was associated with improved PFS (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.22-0.64), followed by Chemo + ICI + ICI (HR 0.66, 95% CI 0.47-0.93) and Chemo + ICI (HR 0.67, 95% CI 0.49-0.91). The most beneficial effect on OS was observed with Chemo + Bev + ICI (HR 0.50, 95% CI 0.34-0.73), followed by Chemo + ICI + ICI (HR 0.64, 95% CI 0.48-0.87) and Chemo + ICI (HR 0.72, 95% CI 0.56-0.92). Regarding OS in wild-type KRAS, ICI + ICI (HR 0.73, 95% CI 0.50-1.07) produced the most favorable effects, followed by Chemo + ICI (HR 0.79, 95% CI 0.63-0.99).
Conclusion: The efficacy of Chemo + Bev + ICI is potentially high for improving PFS and OS in KRAS-mutant NSCLC. In advanced NSCLC, the presence or absence of KRAS mutations may need to be considered when administering first-line treatment.
背景：由于各种分子靶向疗法和免疫检查点抑制剂（ICIs）的出现，晚期非小细胞肺癌（NSCLC）治疗的最新进展大大改善了初治结果。然而，对于克氏大鼠肉瘤病毒抗原（KRAS）突变，索托拉西等分子靶向药物并不适用于一线治疗，最佳的初治方法仍不明确。因此，我们旨在研究 ICI 联合疗法作为 KRAS 突变 NSCLC 一线治疗的疗效：我们对提供晚期NSCLC中KRAS突变状态数据的3期随机对照试验（RCT）进行了系统检索。主要终点是无进展生存期（PFS）和总生存期（OS）。研究人员进行了随机效应网络荟萃分析，对各治疗组进行直接和间接比较：有六项研究符合纳入条件。在针对KRAS突变型NSCLC的网络荟萃分析中，化疗+贝伐单抗（Bev）+ ICI与PFS的改善相关（危险比[HR]0.38，95%置信区间[CI]0.22-0.64），其次是化疗+ICI+ ICI（HR 0.66，95% CI 0.47-0.93）和化疗+ICI（HR 0.67，95% CI 0.49-0.91）。化疗+Bev+ICI（HR 0.50，95% CI 0.34-0.73）对OS的影响最大，其次是化疗+ICI+ICI（HR 0.64，95% CI 0.48-0.87）和化疗+ICI（HR 0.72，95% CI 0.56-0.92）。关于野生型KRAS的OS，ICI + ICI（HR 0.73，95% CI 0.50-1.07）产生的效果最好，其次是化疗 + ICI（HR 0.79，95% CI 0.63-0.99）：结论：化疗+Bev+ICI对改善KRAS突变型NSCLC的PFS和OS有很高的潜在疗效。对于晚期NSCLC患者，在进行一线治疗时可能需要考虑是否存在KRAS突变。
期刊介绍：
Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society.
The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.
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