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 thirdline 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.

The potential therapeutic regimen for overcoming resistance to osimertinib due to rare mutations in NSCLC

“…To the best of our knowledge, disturbances in the PI3K/Akt/mTOR pathway play a central role in lung cancer, with one of most common deregulations being PIK3CA (which encodes for the catalytic subunit p110α of PI3K) mutations, 16 which has already been confirmed to be an important resistance mechanism associated with osimertinib treatment, especially PIK3CA (H1047R) mutation. 17 , 18 , 19 We further assessed whether PIK3CA mutation also regulated acquired resistance to osimertinib in these cells. Subsequently, the PIK3CA (H1047R) mutant Ba/F3 and NSCLC cell lines were constructed, and we also observed increased PI3K (p110α) expression and Akt/mTOR signaling pathway activation in PIK3CA mutant cells ( Figure 2 C).…”

Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor for lung adenosquamous cell carcinoma harboring EGFR mutation: a retrospective study and pooled analysis

“…Our study primarily focused on the initial efficacy of EGFR-TKI in ASC patients. EGFR-TKI acquired resistance in lung ASC is gradually becoming a research hotspot ( 24 ). The progression and resistance mechanisms, including the frequency of T790M mutations, are undoubtedly crucial and future studies focusing on this aspect would indeed be valuable.…”

Comprehensive analyses of genomic features and mutational signatures in adenosquamous carcinoma of the lung

“…However, in contrast to our findings, a lower prevalence of EGFR mutations, 13%, has been reported for lung ASC in the Caucasian ethnic group ( 18 ). Several case studies have indicated good therapeutic responses in patients taking EGFR inhibitors ( 19 – 21 ). In our study, EGFR mutations occur in 83.72% (36/43) of non-smokers and EGFR mutations occur in 25% of smokers, suggesting that the high proportion of patients with harboring EGFR mutations is due to the high proportion of non-smokers.…”