Xu Yanjun, Chen Kaiyan, Xu Yujin, Li Hui, Huang Zhiyu, Lu Hongyang, Huang Dingzhi, Yu Sizhe, Han Na, Gong Lei, Qin Jing, Chen Jun, Xie Fajun, Hong Wei, Lin Xiao, Cheng Fengzhuo, Luo Xiaojie, Fan Yun
Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China.
Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China.
Lancet Oncol. 2025 Jan;26(1):74-84. doi: 10.1016/S1470-2045(24)00643-0.
Brain metastases are a common complication in patients with non-small-cell lung cancer (NSCLC) lacking actionable driver mutations, with limited treatment options and poor prognosis. We aimed to investigate the efficacy and safety of brain radiotherapy combined with camrelizumab and platinum-doublet chemotherapy in patients with newly diagnosed advanced NSCLC and brain metastases.
This multicentre, single-arm, phase 2 trial was done across nine tertiary hospitals in China. Eligible patients were aged 18 years or older, had newly diagnosed brain metastases from NSCLC with no actionable driver mutations (EGFR, ALK, or ROS1), and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients were treated with stereotactic radiosurgery or whole-brain radiotherapy combined with camrelizumab (200 mg intravenously once every 3 weeks) and investigator-selected platinum-doublet chemotherapy (pemetrexed 500 mg/m plus platinum [carboplatin, area under curve (AUC) of 5, or cis-platinum 75 mg/m] for non-squamous NSCLC, and nab-paclitaxel 260 mg/m plus platinum [carboplatin AUC 5, or cis-platinum 75 mg/m] for squamous NSCLC) for four to six cycles. Patients with controlled disease then received maintenance treatment with camrelizumab alone (200 mg intravenously once every 3 weeks; for squamous NSCLC) or camrelizumab plus pemetrexed (500 mg/m every 3 weeks; for non-squamous NSCLC). The primary endpoint was 6-month progression-free survival rate in the full analysis set, which included all patients who received at least one dose of study treatment regardless of whether they had measurable brain lesions per RECIST 1.1. The trial was registered with ClinicalTrials.gov, NCT04291092, and is ongoing.
Between May 6, 2020, and Jan 30, 2023, 67 patients were assessed for eligibility. Two patients were excluded (brain lesions less than 5 mm) and 65 patients were enrolled and treated. Median age was 66 years (IQR 62-70). 60 (92%) of 65 patients were male and five (8%) were female. All 65 patients were Han Chinese. 50 (77%) of 65 patients had non-squamous NSCLC and 46 (71%) were symptomatic. The 6-month progression-free survival rate was 71·7% (95% CI 58·9-81·1) during the median follow-up of 14·1 months (IQR 9·0-20·3; data cutoff Dec 13, 2023). The most common grade 3-4 treatment-related adverse events were decreased neutrophil count (14 [22%] of 65 patients), decreased white blood cell count (ten [15%]), decreased platelet count (ten [15%]), and decreased lymphocyte count (nine [14%]). Neurological toxic effects of grade 3 occurred in three (5%) of 65 patients. Radiation necrosis occurred in three (5%) of 65 patients; all were grade 1 or 2. There were no treatment-related deaths.
Brain radiotherapy combined with camrelizumab and platinum-doublet chemotherapy shows promising efficacy and manageable toxicity and could be a potential treatment option for patients with brain metastases from NSCLC. Randomised controlled trials will be required to confirm these findings.
Beijing Xisike Clinical Oncology Research Foundation and Jiangsu Hengrui Pharmaceuticals.
For the Chinese translation of the abstract see Supplementary Materials section.
脑转移是缺乏可操作驱动基因突变的非小细胞肺癌（NSCLC）患者的常见并发症，治疗选择有限且预后较差。我们旨在研究脑放疗联合卡瑞利珠单抗和铂类双药化疗在新诊断的晚期NSCLC合并脑转移患者中的疗效和安全性。
本多中心、单臂、2期试验在中国9家三级医院开展。符合条件的患者年龄在18岁及以上，新诊断为NSCLC脑转移且无可操作的驱动基因突变（EGFR、ALK或ROS1），东部肿瘤协作组体能状态为0或1。符合条件的患者接受立体定向放射外科或全脑放疗，联合卡瑞利珠单抗（200mg静脉注射，每3周1次）和研究者选择的铂类双药化疗（非鳞状NSCLC用培美曲塞500mg/m²加铂类[卡铂，曲线下面积（AUC）为5，或顺铂75mg/m²]，鳞状NSCLC用白蛋白结合型紫杉醇260mg/m²加铂类[卡铂AUC 5，或顺铂75mg/m²]），共4至6个周期。疾病得到控制的患者随后接受单药卡瑞利珠单抗（200mg静脉注射，每3周1次；用于鳞状NSCLC）或卡瑞利珠单抗联合培美曲塞（每3周500mg/m²；用于非鳞状NSCLC）维持治疗。主要终点是全分析集的6个月无进展生存率，全分析集包括所有接受至少一剂研究治疗的患者，无论其根据RECIST 1.1标准是否有可测量的脑病灶。该试验已在ClinicalTrials.gov注册，注册号为NCT04291092，目前正在进行中。
2020年5月6日至2023年1月30日期间，67例患者接受了资格评估。2例患者被排除（脑病灶小于5mm），65例患者入组并接受治疗。中位年龄为66岁（四分位间距62 - 70岁）。65例患者中60例（92%）为男性，5例（8%）为女性。65例患者均为汉族。65例患者中50例（77%）为非鳞状NSCLC，46例（71%）有症状。在中位随访14.1个月（四分位间距9.0 - 20.3个月；数据截止于2023年12月13日）期间，6个月无进展生存率为71.7%（95%CI 58.9 -
81.1）。最常见的3 - 4级治疗相关不良事件为中性粒细胞计数减少（65例患者中有14例[22%]）、白细胞计数减少（10例[15%]）、血小板计数减少（10例[15%]）和淋巴细胞计数减少（9例[14%]）。65例患者中有3例（5%）发生3级神经毒性作用。65例患者中有3例（5%）发生放射性坏死；均为1级或
2级。没有与治疗相关的死亡。
脑放疗联合卡瑞利珠单抗和铂类双药化疗显示出有前景的疗效和可管理的毒性，可能是NSCLC脑转移患者的一种潜在治疗选择。需要进行随机对照试验来证实这些发现。
北京希思科临床肿瘤学研究基金会和江苏恒瑞医药股份有限公司。
中文翻译摘要见补充材料部分。
