Yonghui Wu,1,* Kai Zhang,1,* Jiexia Guan,2 Weibin Wu,1 Jian Zhang,1 Huiguo Chen1 1Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 2Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huiguo ChenDepartment of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road NO. 600, Guangzhou, Guangdong, 510630, People’s Republic of ChinaEmail Andychen820727@hotmail.comAbstract: 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
