Qi Wenbo, Xi Dayong, Bai Yuping, Liu Le, Ma Yanling, Yin Zhenyu, Chen Hao
The Second Clinical Medical College of Lanzhou University, Lanzhou, China.
Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, China.
Front Pharmacol. 2023 Jan 12;14:1026135. doi: 10.3389/fphar.2023.1026135. eCollection 2023.
Lung cancer is a major public health issue and an enormous burden on society in China. Most lung cancers occur in elderly patients with non-small cell lung cancer (NSCLC), and many factors limit their treatment options. Chemotherapy-free therapy can avoid psychological fear, treatment pain, and adverse reactions caused by chemotherapy. Patients with non-small cell lung cancer with tumour protein p53 () gene mutations or Kirsten rat sarcoma viral oncogene homologue () gene mutations tend to be more sensitive to anlotinib or programmed cell death protein 1 (PD-1) drugs. However, Kirsten rat sarcoma viral oncogene homologue is a proto-oncogene downstream of the epidermal growth factor receptor () gene; therefore, if the Kirsten rat sarcoma viral oncogene homologue gene has an activating mutation, EGFR-targeted drug resistance may occur. Further studies are needed to explore whether patients with dual Kirsten rat sarcoma viral oncogene homologue and tumour protein p53 mutations can be treated with targeted immunotherapy without chemotherapy. A 74-year-old man was referred to the Lanzhou University Second Hospital due to chest tightness, shortness of breath, and weight loss for 2 months and was diagnosed with moderately to poorly differentiated adenocarcinoma. Laboratory examinations showed increased alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)-125, and CA199 levels, and gene sequencing indicated mutations in Kirsten rat sarcoma viral oncogene homologue and tumour protein p53. Immunohistochemical analysis showed positive PD-L1 and PD-1 expression. Peripheral blood immune checkpoint test using flow cytometry indicated that the PD-1 + CD8 levels were positive. After multi-disciplinary treatment, therapy with a combination of anlotinib and camrelizumab was initiated. Camrelizumab 200 mg was administered intravenously once every 3 weeks. Anlotinib 12 mg was administered orally daily before breakfast for 2 weeks with a week of rest in every cycle of 21 days. A reduction in alpha-fetoprotein, carcinoembryonic antigen, CA125, CA199, and CA724 levels was observed up to the first cycle, which decreased within the normal limits up to the second cycle and continued until the eighteenth cycle. The patient's chest tightness, shortness of breath, weight loss, and other symptoms significantly improved following treatment. Computed tomography imaging showed that the neoplastic lesion was dramatically reduced. The patient is currently being followed-up for more than 2 years to evaluate the duration of the response. Chemotherapy-free immunotherapy combined with targeted therapy is an effective treatment for advanced non-small cell lung cancer in elderly patients with Kirsten rat sarcoma viral oncogene homologue and tumour protein p53 mutations. Such therapies should be supported with further clinical studies with larger sample sizes.
肺癌是中国一个重大的公共卫生问题，给社会带来了巨大负担。大多数肺癌发生在患有非小细胞肺癌（NSCLC）的老年患者中，许多因素限制了他们的治疗选择。免化疗疗法可以避免化疗引起的心理恐惧、治疗痛苦和不良反应。患有肿瘤蛋白p53（）基因突变或 Kirsten 大鼠肉瘤病毒癌基因同源物（）基因突变的非小细胞肺癌患者往往对安罗替尼或程序性细胞死亡蛋白1（PD-1）药物更敏感。然而，Kirsten大鼠肉瘤病毒癌基因同源物是表皮生长因子受体（）基因下游的原癌基因；因此，如果 Kirsten 大鼠肉瘤病毒癌基因同源物基因发生激活突变，可能会出现表皮生长因子受体靶向药物耐药。需要进一步研究来探索同时患有 Kirsten 大鼠肉瘤病毒癌基因同源物和肿瘤蛋白p53突变的患者是否可以接受无化疗的靶向免疫治疗。一名74岁男性因胸闷、气短和体重减轻2个月被转诊至兰州大学第二医院，被诊断为中低分化腺癌。实验室检查显示甲胎蛋白（AFP）、癌胚抗原（CEA）、癌抗原（CA）-125和CA199水平升高，基因测序表明 Kirsten 大鼠肉瘤病毒癌基因同源物和肿瘤蛋白p53发生突变。免疫组化分析显示PD-L1和PD-1表达呈阳性。使用流式细胞术进行外周血免疫检查点检测表明PD-1 + CD8水平呈阳性。经过多学科治疗后，开始使用安罗替尼和卡瑞利珠单抗联合治疗。卡瑞利珠单抗200mg每3周静脉注射一次。安罗替尼12mg每天早餐前口服，持续2周，每21天为一个周期，中间休息1周。在第一个周期时观察到甲胎蛋白、癌胚抗原、CA125、CA199和CA724水平下降，到第二个周期时降至正常范围，并持续到第18个周期。治疗后患者的胸闷、气短、体重减轻等症状明显改善。计算机断层扫描成像显示肿瘤病灶显著缩小。目前该患者正在接受超过2年的随访，以评估缓解持续时间。免化疗免疫治疗联合靶向治疗是治疗患有 Kirsten 大鼠肉瘤病毒癌基因同源物和肿瘤蛋白p53突变的老年晚期非小细胞肺癌的有效方法。此类疗法应通过更大样本量的进一步临床研究予以支持。
