背景:肺癌,占全球癌症病例和死亡的很大比例,造成相当大的健康负担。非小细胞肺癌(NSCLC)患者由于晚期诊断和耐药性,预后差,治疗选择有限。丝裂原活化蛋白激酶(MAPK)通路失调,这与NSCLC的发病机理有关,强调了MEK抑制剂如比米替尼的潜力。尽管在其他癌症中有希望的结果,目前尚缺乏评价比米替尼治疗肺癌的安全性和有效性的综合性研究.本系统评价旨在探讨比米替尼治疗肺癌的安全性和有效性。
方法:我们搜索了PubMed,Scopus,WebofScience,和谷歌学者,直到2023年9月。纳入了评价比米替尼治疗肺癌疗效或安全性的临床试验。如果研究包括与肺癌无关的个体,则将其排除在外。调查了其他治疗方法,或者有不同类型的设计。使用美国国立卫生研究院工具进行质量评估。
结果:共纳入了228名参与者的7项研究。四个人有很好的质量判断,三个人有公平的质量判断。大多数患者经历了全因不良事件,腹泻,疲劳,恶心是任何级别中最常见的不良事件。客观反应率(ORR)高达75%,中位无进展生存期(PFS)为9.3个月.24周后的疾病控制率从41%到64%不等。总生存期(OS)介于3.0和18.8个月之间。值得注意的是,在超过50%的患者中观察到与治疗相关的不良事件,包括严重的不良事件,如结肠炎,发热性中性粒细胞减少症,和肺部感染。在五项研究中,一些不良事件导致剂量限制和药物停药。此外,五项研究报告了死亡病例,主要是由于疾病进展。中位治疗时间为14.8周至8.4个月。比米替尼最常见的剂量是30毫克或45毫克,每天两次,有时与恩科拉非尼或羟氯喹等其他药物联合使用。
结论:只有少数研究表明比尼是有效的,在改进操作系统方面,PFS,和ORR,而大多数研究发现,与传统化疗相比,比米替尼在肺癌患者中的疗效不显著,毒性增加。建议进一步开展大规模随机对照试验。
BACKGROUND: Lung cancer, accounting for a significant proportion of global cancer cases and deaths, poses a considerable health burden. Non-small cell lung cancer (NSCLC) patients have a poor prognosis and limited treatment options due to late-stage diagnosis and drug resistance. Dysregulated of the mitogen-activated protein kinase (MAPK) pathway, which is implicated in NSCLC pathogenesis, underscores the potential of MEK inhibitors such as binimetinib. Despite promising results in other cancers, comprehensive studies evaluating the safety and efficacy of binimetinib in lung cancer are lacking. This systematic review aimed to investigate the safety and efficacy of binimetinib for lung cancer treatment.
METHODS: We searched PubMed, Scopus, Web of Science, and Google Scholar until September 2023. Clinical trials evaluating the efficacy or safety of binimetinib for lung cancer treatment were included. Studies were excluded if they included individuals with conditions unrelated to lung cancer, investigated other treatments, or had different types of designs. The quality assessment was conducted utilizing the National Institutes of Health tool.
RESULTS: Seven studies with 228 participants overall were included. Four had good quality judgments, and three had fair quality judgments. The majority of patients experienced all-cause adverse events, with diarrhea, fatigue, and nausea being the most commonly reported adverse events of any grade. The objective response rate (ORR) was up to 75%, and the median progression-free survival (PFS) was up to 9.3 months. The disease control rate after 24 weeks varied from 41% to 64%. Overall survival (OS) ranged between 3.0 and 18.8 months. Notably, treatment-related adverse events were observed in more than 50% of patients, including serious adverse events such as colitis, febrile neutropenia, and pulmonary infection. Some adverse events led to dose limitation and drug discontinuation in five studies. Additionally, five studies reported cases of death, mostly due to disease progression. The median duration of treatment ranged from 14.8 weeks to 8.4 months. The most common dosage of binimetinib was 30 mg or 45 mg twice daily, sometimes used in combination with other agents like encorafenib or hydroxychloroquine.
CONCLUSIONS: Only a few studies have shown binimetinib to be effective, in terms of improving OS, PFS, and ORR, while most of the studies found nonsignificant efficacy with increased toxicity for binimetinib compared with traditional chemotherapy in patients with lung cancer. Further large-scale randomized controlled trials are recommended.