Abstract: Concurrent mutations of epidermal growth factor receptor (EGFR) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in non-small cell lung cancer (NSCLC) are rare, and the presence of concurrent mutations may complicate treatment. Herein, we report a case of primary lung adenosquamous carcinoma with concurrent EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations, and the results of a literature review to help management and treatment. A 49-year-old female was admitted our department for coughing and excessive sputum production for more than 1 month. Computed tomography (CT) of the chest identified a lesion, and a CT-guided needle biopsy was performed. Pathological examination and immunohistochemistry (IHC) staining confirmed a diagnosis of primary lung adenosquamous carcinoma. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) gene sequencing demonstrated mutations in both EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations in adenocarcinoma (AC) component. She was treated with pemetrexed plus platinum-based chemotherapy and an EGFR-tyrosine kinase inhibitor (TKI). Disease progression occurred with gefitinib or osimertinib as maintenance therapy. A repeat CT-guided needle biopsy was performed, and generation sequencing (NGS) revealed EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations. Anlotinib monotherapy was then administered as the third-line treatment, and there was a PR. The patient is currently still receiving treatment and follow-up. To our knowledge, there is little evidence that anlotinib is beneficial when there are concurrent EGFR and PIK3CA mutations. PIK3CA mutations are associated with poor therapeutic effects and short survival time. Concurrent EGFR and PIK3CA mutations do not respond to EGFR-TKI treatment. Chemotherapy should be given in combination with a TKI and can prolong the progression-free survival (PFS) and overall survival (OS) of patients with lung cancer.

Keywords: EGFR mutation, PIK3CA mutation, resistant mutation, adenosquamous carcinoma, anlotinib

中文翻译：

---

EGFR 和 PIK3CA 突变的肺腺鳞癌化疗后使用安罗替尼治疗和 EGFR-TKI 耐药：病例报告和文献综述

摘要：非小细胞肺癌 (NSCLC) 中表皮生长因子受体 (EGFR) 和磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚基 α (PIK3CA) 的并发突变很少见，并发突变的存在可能会复杂化。治疗。在此，我们报告了一例并发EGFR 21 (L858R) 和PIK3CA的原发性肺腺鳞癌病例(H1047R/E545K) 突变，以及有助于管理和治疗的文献综述结果。女性，49岁，因咳嗽多痰1个月以上来我科就诊。胸部计算机断层扫描 (CT) 确定了病变，并进行了 CT 引导的针刺活检。病理检查和免疫组织化学 (IHC) 染色证实了原发性肺腺鳞癌的诊断。扩增难治性突变系统-聚合酶链反应 (ARMS-PCR) 基因测序证实了EGFR 21 (L858R) 和PIK3CA 中的突变(H1047R/E545K) 腺癌 (AC) 成分中的突变。她接受了培美曲塞加铂类化疗和 EGFR-酪氨酸激酶抑制剂 (TKI) 的治疗。吉非替尼或奥希替尼作为维持治疗发生疾病进展。进行了重复 CT 引导针活检，世代测序 (NGS) 显示EGFR 21 (L858R) 和PIK3CA (H1047R/E545K) 突变。然后将安罗替尼单药治疗作为三线治疗，并且获得了 PR。目前，患者仍在接受治疗和随访。据我们所知，几乎没有证据表明安罗替尼在同时存在EGFR和PIK3CA时有益突变。PIK3CA 突变与治疗效果差和存活时间短有关。同时发生的EGFR和PIK3CA突变对 EGFR-TKI 治疗没有反应。化疗应与 TKI 联合使用，可延长肺癌患者的无进展生存期 (PFS) 和总生存期 (OS)。

关键词： EGFR突变，PIK3CA突变，耐药突变，腺鳞癌，安罗替尼