Li Meihui, Qin Jing, Xie Fajun, Gong Lei, Han Na, Lu Hongyang
Zhejiang Key Laboratory of Diagnosis & Treatment Technology On Thoracic Oncology (Lung and Esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, Hangzhou, P. R. China.
Department of Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, Hangzhou, P. R. China.
Discov Oncol. 2022 Aug 9;13(1):72. doi: 10.1007/s12672-022-00537-7.
Osimertinib, a mutant-specific third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is emerging as the preferred first-line of treatment for EGFR-mutant lung cancer. However, osimertinib resistance inevitably develops among patients treated with the drug. The modal resistance mechanisms of osimertinib include the occurrence of epithelial transition factor (c-MET) amplification and C797S mutation, whereas rare mutations are presented as case reports. Recently, the L718Q/V mutation in exon 18 of EGFR has been reported to contribute to one of the possible mechanisms of resistance. The clinical features and subsequent treatment strategies for this mutation require further research. This study retrospectively enrolled NSCLC patients with the L718Q/V mutation from 2017 to 2021 at the Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), as well as additional patients with the same mutation from PubMed literature, to summarize the clinical features of the mutation. The association between the detection of L718Q/V and resistance to osimertinib, as well as impacts on the therapeutic process and outcome, was analyzed. We included a total of two patients diagnosed at Zhejiang Cancer Hospital and twelve patients from the literature. Of the fourteen total patients, 64.3% were male and 35.7% were female. The average age of the group was 60.2 years (range 45-72). A history of tobacco use was common among the group. In all of the cases we considered, the L718Q/V mutation was secondary to the L858R mutation. The second-generation TKI afatinib was found to provide a high disease control rate (DCR) (85.7%, 6/7) and relatively low objective response rate (ORR) (42/9%, 3/7). The median progression free survival (mPFS) for this treatment reached 2 months (1-6 months). The patients failed to benefit from chemotherapy combined with immunotherapy or other TKI medications. Due to the limited number of cases considered in this study, future studies should explore drugs that more precisely target the L718Q/V mutation of EGFR exon 18.
奥希替尼是一种针对特定突变的第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI），正逐渐成为EGFR突变型肺癌的首选一线治疗药物。然而，接受该药物治疗的患者不可避免地会出现奥希替尼耐药。奥希替尼的主要耐药机制包括上皮转换因子（c-MET）扩增和C797S突变，而罕见突变则以病例报告的形式呈现。最近，有报道称EGFR第18外显子的L718Q/V突变是可能的耐药机制之一。该突变的临床特征及后续治疗策略有待进一步研究。本研究回顾性纳入了2017年至2021年在中国科学院大学附属肿瘤医院（浙江省肿瘤医院）确诊的携带L718Q/V突变的非小细胞肺癌患者，以及从PubMed文献中纳入的其他携带相同突变的患者，以总结该突变的临床特征。分析了L718Q/V检测与奥希替尼耐药之间的关联，以及对治疗过程和结果的影响。我们共纳入了两名在浙江省肿瘤医院确诊的患者和文献中的12名患者。在这14名患者中，64.3%为男性，35.7%为女性。该组患者的平均年龄为60.2岁（范围45 - 72岁）。该组患者中吸烟史较为常见。在我们考虑的所有病例中，L718Q/V突变继发于L858R突变。发现第二代TKI阿法替尼具有较高的疾病控制率（DCR）（85.7%，6/7）和相对较低的客观缓解率（ORR）（42.9%，3/7）。该治疗的中位无进展生存期（mPFS）达到2个月（1 - 6个月）。患者未能从化疗联合免疫治疗或其他TKI药物中获益。由于本研究纳入的病例数量有限，未来研究应探索更精准靶向EGFR第18外显子L718Q/V突变的药物。
