Zhu Xianmin, Dong Shuang, Tang Jing, Xie Rong, Wu Huijing, Hofman Paul, Mrugala Maciej M, Hu Sheng
Department of Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Laboratory of Clinical and Experimental Pathology, FHU OncoAge, Pasteur Hospital, BB-0033-00025, CHU Nice, Université Côte d'Azur, Nice, France.
Ann Transl Med. 2022 Sep;10(17):942. doi: 10.21037/atm-22-4208.
Immunotherapy has been shown to improve the overall survival (OS) in patients with advanced or metastatic non-small cell lung cancer (NSCLC) without driver gene mutations. However, monotherapy with immunotherapy alone or combined with chemotherapy in NSCLC patients with untreated brain metastases (BM) is still under debate. Data regarding treatment of BM with immunotherapy and temozolomide (TMZ) in patients with NSCLC is rare.
A 60-year-old male due to cough and expectoration presented in our hospital. Chest computed tomography (CT), brain magnetic resonance imaging (MRI) and immunohistochemistry of a mediastinal lymph node biopsy were administered, he was diagnosed with stage IIIB lung adenocarcinoma. Without driver gene mutations, he was treated with platinum-based chemotherapy because he refused to accept concurrent radiation therapy (RT). Heavy cough companied with hemoptysis and chest CT scan both revealed progressive disease (PD) after 6 cycles of chemotherapy. Immunotherapy was consequently considered, while two metastatic lesions in the brain were confirmed after combined treatment of pembrolizumab with docetaxel. TMZ was administered in combination with pembrolizumab (200 mg, day 1). A new metastasis in the right occipital lobe was detected on a scan 1 month later, though the other 2 lesions continued to shrink. The treatment was continued, MRI and CT scans suggested complete response (CR) was achieved for both the BM and lung lesions after 3 cycles. Consolidation therapy with TMZ and pembrolizumab (100 mg) per month was considered for another 7 months. Maintenance monotherapy with pembrolizumab (100 mg) was selected because of his stable CR status. At 59 months since diagnosis, the patient remains alive, with CR for both the primary lesions and BM. The patient experienced slight numbness on each side of his feet. There was no occurrence of adverse effects greater than grade 3.
The data indicates that immunotherapy combined with TMZ for untreated BM in NSCLC patients maybe an efficient and safe decision making therapeutic choice. Despite the encouraging efficacy of the combination, it is an isolated case and the speculation of synergism need to be proved in further pharmacokinetic/pharmacodynamic studies even in large randomized controlled trials.
免疫疗法已被证明可改善无驱动基因突变的晚期或转移性非小细胞肺癌(NSCLC)患者的总生存期(OS)。然而,对于未经治疗的脑转移(BM)NSCLC患者,单独使用免疫疗法或与化疗联合使用仍存在争议。关于NSCLC患者使用免疫疗法和替莫唑胺(TMZ)治疗BM的数据很少。
一名60岁男性因咳嗽、咳痰来我院就诊。进行了胸部计算机断层扫描(CT)、脑部磁共振成像(MRI)以及纵隔淋巴结活检的免疫组织化学检查,诊断为IIIB期肺腺癌。无驱动基因突变,因拒绝接受同步放疗(RT),接受了铂类化疗。6周期化疗后,严重咳嗽伴咯血及胸部CT扫描均显示疾病进展(PD)。因此考虑进行免疫治疗,在帕博利珠单抗联合多西他赛治疗后确认脑部有两个转移病灶。TMZ与帕博利珠单抗(200mg,第1天)联合使用。1个月后扫描发现右侧枕叶有新的转移灶,尽管其他2个病灶持续缩小。继续治疗,MRI和CT扫描显示3周期后BM和肺部病灶均达到完全缓解(CR)。考虑再进行7个月的TMZ和帕博利珠单抗(100mg)巩固治疗。由于其CR状态稳定,选择帕博利珠单抗(100mg)维持单药治疗。自诊断以来59个月,患者仍然存活,原发灶和BM均为CR。患者双足出现轻微麻木。未发生大于3级的不良反应。
数据表明,免疫疗法联合TMZ治疗未经治疗的NSCLC患者BM可能是一种有效且安全的治疗选择。尽管联合治疗的疗效令人鼓舞,但这是一个孤立病例,即使在大型随机对照试验中,协同作用的推测也需要在进一步的药代动力学/药效学研究中得到证实。