Zhai Xiaoqian, Liu Jiewei, Liang Zuoyu, Li Zhixi, Liu Yanyang, Huang Lin, Wang Weiya, Luo Feng
Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Pathology Department, West China Hospital, Sichuan University, Chengdu, China.
Front Oncol. 2021 Jun 24;11:661034. doi: 10.3389/fonc.2021.661034. eCollection 2021.
The treatment sequence of immunotherapy (IO) and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is of great importance for the survival of non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutation. Here, we reported an advanced lung adenocarcinoma case concurrent with EGFR sensitive mutation and high PD-L1 expression (>50%) that was administrated with gefitinib firstly, and then became resistant to EGFR-TKI. He received the strategy of immunity-combined chemo-radiotherapy and responded significantly. However, the disease re-progressed after 10 months. Surprisingly, the tumor re-sensitized to gefitinib for 13 months. At final, following the treatment pressure of TKI-IO combination therapy-TKI strategy, tumor clone eventually transformed into small cell lung carcinoma (SCLC). For one thing, our study provided novel approach and extended the treatment spectra of overcoming immunotherapy resistance after EGFR resistance in driver oncogene-mutated NSCLC. For another thing, our case is the first time to report that SCLC transformation can be achieved after gefitinib-pembrolizumab-gefitinib resistance in EGFR sensitive mutation NSCLC, providing a new condition for SCLC transformation.
免疫疗法（IO）和表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）的治疗顺序对于具有EGFR敏感突变的非小细胞肺癌（NSCLC）患者的生存至关重要。在此，我们报告了一例晚期肺腺癌病例，该病例同时存在EGFR敏感突变和高PD-L1表达（>50%），首先接受吉非替尼治疗，随后对EGFR-TKI耐药。他接受了免疫联合放化疗策略并取得显著反应。然而，10个月后疾病再次进展。令人惊讶的是，肿瘤对吉非替尼再次敏感达13个月。最终，在TKI-IO联合治疗-TKI策略的治疗压力下，肿瘤克隆最终转化为小细胞肺癌（SCLC）。一方面，我们的研究提供了新方法，扩展了驱动癌基因突变的NSCLC中EGFR耐药后克服免疫治疗耐药的治疗谱。另一方面，我们的病例首次报道了在EGFR敏感突变的NSCLC中吉非替尼-帕博利珠单抗-吉非替尼耐药后可实现SCLC转化，为SCLC转化提供了新情况。
