Luo Yuxi, Wei Jianping, Zhang Jing, Zeng Liangtao, Zeng Zhimin, Liu Anwen
Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Jiangxi Key Laboratory of Clinical Translational Cancer Research, Nanchang, Jiangxi Province, China.
Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
Lung Cancer. 2021 May;155:170-174. doi: 10.1016/j.lungcan.2021.03.019. Epub 2021 Mar 26.
Pulmonary pleomorphic carcinoma (PPC) is a rare and highly malignant subtype of non-small-cell lung cancer (NSCLC), and chemotherapy and radiotherapy are insensitive. Some clinical trials have shown that targetable driver gene mutations, such as EGFR, ALK or BRAF, have rarely been detected in PPC patients, but the incidence of MET exon 14 mutations is more frequent. For these patients with driver gene mutations, corresponding molecular targeted therapy may be valid. In addition, limited cases have suggested that immunotherapy may be effective for PPC without sensitising EGFR or ALK alterations, but the efficacy in patients with other driver mutations remains unclear. Herein, we reported two PPC patients with different targetable gene mutations who both responded dramatically to the PD-1 inhibitor camrelizumab combined with the oral anti-angiogenic drug anlotinib: one harbouring a BRAF V600E mutation with positive PD-L1 expression, few tumour-infiltrating lymphocytes (TILs) and abundant tumour blood vessels; and the other exhibiting a MET exon 14 skipping mutation with PD-L1 overexpression, scattered TILs and abundant tumour blood vessels. Our findings suggest that PD-1 inhibitor combined with anlotinib may be a potential treatment for PPC patients, and abundant tumour vessels should be investigated as a possible therapeutic biomarker.
肺多形性癌(PPC)是一种罕见且高度恶性的非小细胞肺癌(NSCLC)亚型,化疗和放疗对此不敏感。一些临床试验表明,在PPC患者中很少检测到可靶向的驱动基因突变,如EGFR、ALK或BRAF,但MET外显子14突变的发生率更高。对于这些具有驱动基因突变的患者,相应的分子靶向治疗可能有效。此外,有限的病例表明,免疫疗法可能对无EGFR或ALK改变的PPC有效,但对其他驱动基因突变患者的疗效仍不清楚。在此,我们报告了两名具有不同可靶向基因突变的PPC患者,他们对PD-1抑制剂卡瑞利珠单抗联合口服抗血管生成药物安罗替尼均有显著反应:一名患者携带BRAF V600E突变,PD-L1表达阳性,肿瘤浸润淋巴细胞(TILs)较少且肿瘤血管丰富;另一名患者表现为MET外显子14跳跃突变,PD-L1过表达,TILs散在分布且肿瘤血管丰富。我们的研究结果表明,PD-1抑制剂联合安罗替尼可能是PPC患者的一种潜在治疗方法,应将丰富的肿瘤血管作为一种可能的治疗生物标志物进行研究。