Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
Ann Palliat Med. 2021 Mar;10(3):3469-3474. doi: 10.21037/apm-19-462. Epub 2020 Sep 21.
Extensive clinical studies have indicated that the epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKIs) can significantly improve the survival rate of patients with EGFRmutation-positive malignancies. However, acquired resistance to the third-generation EGFR-TKI osimertinib is an intractable obstacle for many clinical oncologists. The resistance mechanism of osimertinib is very complicated, and the individual treatment varies greatly. We present the case of a 76-year-old woman with advanced non-small cell lung cancer (NSCLC) with EGFR L858R mutation, as well as multiple lung metastases and multiple liver metastases. The patient's lung lesions progressed after almost 2 years of treatment with Osimertinib. Due to poor physical condition, she could not tolerate chemotherapy or invasive examination. A next-generation sequencing (NGS) panel of a plasma sample showed missense mutations of KRAS (G12S), MET (D1028Y), AR (S697P), LRP1B (S2662C) with allelic frequencies of 0.6%, 0.5%, 0.2%, 0.2%, respectively), 2 nonsense mutations [ZNF521 (E307*), MET (Q42*), with allelic frequencies of 0.5%, 0.3%, respectively], and a splicing mutation in FAT1 (c.3266-1G>C) with an allelic frequency of 0.5%. After treatment with camrelizumab (200 mg fortnightly) combined with small dose of apatinib (125 mg qd), the patient's lung lesions were successfully overcome with significant reduction and necrosis formation. And the patient's symptoms were significantly relieved and was well tolerated. To our knowledge, this is the first report on the successful treatment of such patients. It indicated a promising treatment option in the clinic to the NSCLC with osimertinib resistance.
大量临床研究表明，表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）可显著提高 EGFR 突变阳性恶性肿瘤患者的生存率。然而，第三代 EGFR-TKI 奥希替尼的获得性耐药是许多临床肿瘤学家的一个棘手难题。奥希替尼的耐药机制非常复杂，个体治疗差异很大。我们报告了一例 76 岁女性晚期非小细胞肺癌（NSCLC）患者，该患者 EGFR L858R 突变，并有多个肺转移和多个肝转移。该患者在接受奥希替尼治疗近 2 年后肺部病变进展。由于身体状况不佳，她无法耐受化疗或有创检查。一份血浆样本的下一代测序（NGS）面板显示 KRAS（G12S）、MET（D1028Y）、AR（S697P）、LRP1B（S2662C）的错义突变，等位基因频率分别为 0.6%、0.5%、0.2%、0.2%），2 个无义突变[ZNF521（E307*）、MET（Q42*），等位基因频率分别为 0.5%、0.3%]，以及 FAT1（c.3266-1G>C）剪接突变，等位基因频率为 0.5%。接受卡瑞利珠单抗（200mg 每两周）联合小剂量阿帕替尼（125mg 每日）治疗后，患者肺部病变成功得到控制，显著缩小并发生坏死。且患者症状明显缓解，且耐受良好。据我们所知，这是首例成功治疗此类患者的报告。为奥希替尼耐药的 NSCLC 患者提供了一种有前途的临床治疗选择。
