Treatment with Anlotinib After Chemotherapy and EGFR-TKI Resistance in Lung Adenosquamous Carcinoma with Concurrent EGFR and PIK3CA Mutations: A Case Report and Literature Review

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

Acknowledgments

We would like to thank the patient and her family for giving consent for publication.

Abbreviations

EGFR, epidermal growth factor receptor; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; NSCLC, non-small cell lung cancer; CT, computed tomography; IHC, immunohistochemistry; ARMS-PCR, amplification refractory mutation system – polymerase chain reaction; AC, adenocarcinoma; TKI, tyrosine kinase inhibitor; PR, partial response; PD, progression disease; NGS, next-generation sequencing; PFS, progression-free survival; OS, overall survival; PET-CT, positron emission tomography-CT; MRI, brain magnetic resonance imaging; SCC, squamous cell carcinoma; SD, steady disease; mPFS, median PFS; ORR, objective response rate.

Data Sharing Statement

For patients’ privacy, the patient information is publicly inaccessible.

Ethics Approval and Consent to Participate

This study was approved by institutional ethics committee of Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. Written informed consent to participate was obtained from the patient.

Consent for Publication

Written informed consent for publication has been obtained from the patient stating that the details/images can be available on the Internet and may be seen by the general public.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agreed to be accountable for all aspects of the work.

Disclosure

The authors have no competing interests to declare.