Zhang Chengkai, Zhou Wenjianlong, Zhang Dainan, Ma Shunchang, Wang Xi, Jia Wang, Guan Xiudong, Qian Ke
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China.
Department of Neurosurgery, Beijing Neurosurgical Institute, Beijing 100071, China.
Open Med (Wars). 2023 Feb 14;18(1):20220574. doi: 10.1515/med-2022-0574. eCollection 2023.
More clinical evidence is needed regarding the relative priority of treatments for brain metastases (BMs) from EGFR/ALK-negative/unselected non-small cell lung cancer (NSCLC). PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov databases were searched. Overall survival (OS), central nervous system progression-free survival (CNS-PFS), and objective response rate (ORR) were selected for Bayesian network meta-analyses. We included 25 eligible randomized control trials (RCTs) involving 3,054 patients, investigating nine kinds of treatments for newly diagnosed BMs and seven kinds of treatments for previously treated BMs. For newly diagnosed BMs, adding chemotherapy, EGFR-TKIs, and other innovative systemic agents (temozolomide, nitroglycerin, endostar, enzastaurin, and veliparib) to radiotherapy did not significantly prolong OS than radiotherapy alone; whereas radiotherapy + nitroglycerin showed significantly better CNS-PFS and ORR. Surgery could significantly prolong OS (hazard ratios [HR]: 0.52, 95% credible intervals: 0.41-0.67) and CNS-PFS (HR: 0.32, 95% confidence interval: 0.18-0.59) compared with radiotherapy alone. For previously treated BMs, pembrolizumab + chemotherapy, nivolumab + ipilimumab, and cemiplimab significantly prolonged OS than chemotherapy alone. Pembrolizumab + chemotherapy also showed better CNS-PFS and ORR than chemotherapy. In summary, immune checkpoint inhibitor (ICI)-based therapies, especially ICI-combined therapies, showed promising efficacies for previously treated BMs from EGFR/ALK-negative/unselected NSCLC. The value of surgery should also be emphasized. The result should be further confirmed by RCTs.
对于表皮生长因子受体（EGFR）/间变性淋巴瘤激酶（ALK）阴性/未选择的非小细胞肺癌（NSCLC）脑转移（BMs）的治疗相对优先级，还需要更多临床证据。我们检索了PubMed、EMBASE、科学网、考克兰图书馆和临床试验.gov数据库。选择总生存期（OS）、中枢神经系统无进展生存期（CNS-PFS）和客观缓解率（ORR）进行贝叶斯网络荟萃分析。我们纳入了25项符合条件的随机对照试验（RCT），涉及3054例患者，研究了9种针对新诊断BMs的治疗方法和7种针对既往治疗过的BMs的治疗方法。对于新诊断的BMs，在放疗基础上加用化疗、EGFR酪氨酸激酶抑制剂（EGFR-TKIs）和其他创新的全身治疗药物（替莫唑胺、硝酸甘油、恩度、恩扎妥林和维利帕尼），与单纯放疗相比，并未显著延长OS；而放疗+硝酸甘油显示出显著更好的CNS-PFS和ORR。与单纯放疗相比，手术可显著延长OS（风险比[HR]：0.52，95%可信区间：0.41-0.67）和CNS-PFS（HR：0.32，95%置信区间：0.18-0.59）。对于既往治疗过的BMs，帕博利珠单抗+化疗、纳武利尤单抗+伊匹木单抗和西米普利单抗与单纯化疗相比，显著延长了OS。帕博利珠单抗+化疗也显示出比化疗更好的CNS-PFS和ORR。总之，基于免疫检查点抑制剂（ICI）的疗法，尤其是ICI联合疗法，对既往治疗过的EGFR/ALK阴性/未选择的NSCLC的BMs显示出有前景的疗效。手术的价值也应得到重视。该结果应通过随机对照试验进一步证实。
