The C797S mutation encoded by EGFR exon 20 is classically observed as a tertiary event in EGFR-mutant non-small-cell lung carcinoma (NSCLC) primarily treated by first generation tyrosine kinase inhibitors (TKI) and secondarily treated by third-generation TKI, such as osimertinib, if the EGFR-T790M resistance mutation is detected. Recently, significant prolonged progression free survival has been observed following first-line osimertinib, in EGFR-mutant NSLC. While mechanisms of molecular resistance to first-generation TKI have been well studied, little is known about resistance induced by primary third-generation TKI treatments. We report the case of a 65 year-old female treated by first-line osimertinib for a multimetastatic exon 19-EGFR-mutant NSCLC. EGFR-C797S resistance mutation and PIK3CA mutation were detected together with the remaining EGFR-exon 19 deletion. This observation provides insights of acquired resistance to first line-osimertinib. It also highlights the importance of making molecular platforms which perform routine EGFR testing in lung cancer aware of the kind of therapeutic protocols given to the patient. Indeed, for rapid results or low-costs procedures, some targeted methods specifically targeting T790M may be used at relapse and may overlook alterations such as C797S or PIK3CA mutations. Targeted next generation sequencing is therefore a recommended option.

由 EGFR 外显子 20 编码的 C797S 突变在 EGFR 突变非小细胞肺癌 (NSCLC) 中被经典观察为主要由第一代酪氨酸激酶抑制剂 (TKI) 治疗并由第三代 TKI 二次治疗的三级事件，例如如奥希替尼，如果检测到 EGFR-T790M 耐药突变。最近，在EGFR突变的 NSLC 中，一线奥希替尼后观察到显着延长的无进展生存期。虽然对第一代 TKI 的分子耐药机制已得到充分研究，但对由初级第三代 TKI 治疗引起的耐药性知之甚少。我们报告了一名 65 岁女性接受一线奥希替尼治疗多转移外显子 19- EGFR 的病例-突变的非小细胞肺癌。EGFR-C797S抗性突变和PIK3CA突变与剩余一起检测EGFR -exon 19删除。这一观察结果提供了对一线奥希替尼获得性耐药的见解。它还强调了使在肺癌中进行常规EGFR检测的分子平台了解给予患者的治疗方案类型的重要性。事实上，为了快速获得结果或低成本程序，一些专门针对 T790M 的靶向方法可能会在复发时使用，并且可能会忽略 C797S 或 PIK3CA 突变等改变。因此，靶向下一代测序是推荐的选择。