# PIK3CA-Mutant Non-Small Cell Lung Cancer Refractory to Two Lines of Chemoimmunotherapy: A Case Report

## TL;DR

A case report shows that PIK3CA-mutant non-small cell lung cancer may not respond well to standard chemoimmunotherapy treatments.

## Contribution

This case highlights the poor response of isolated PIK3CA-mutant NSCLC to chemoimmunotherapy and suggests a need for PI3K-targeted therapies.

## Key findings

- The patient with PIK3CA E545K mutation had rapid disease progression despite two lines of chemoimmunotherapy.
- PIK3CA-mutant NSCLC may be refractory to conventional treatments including CTLA-4 inhibitors.
- The case underscores the need for developing PI3K-targeted therapies for better outcomes.

## Abstract

PIK3CA mutations play a critical role in tumorigenesis by driving constitutive activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. These mutations have been identified in a small subset of non-small cell lung cancer (NSCLC), but their clinical significance and response to chemoimmunotherapy remain unclear. A 44-year-old man with a 24-pack-year smoking history presented with hoarseness and exertional dyspnea. Imaging demonstrated an irregular left upper-lobe pulmonary nodule consistent with the primary lesion, along with metastatic involvement of the left frontal lobe, cervical-mediastinal lymph nodes, right kidney, and lumbar vertebrae. Endobronchial ultrasound-guided transbronchial needle aspiration of the station 4R lymph node confirmed adenosquamous carcinoma. Molecular analysis revealed a PIK3CA E545K mutation without coexisting oncogenic driver alterations. The programmed cell death ligand 1 tumor proportion score indicated low expression (1-9%). Despite first-line carboplatin, nab-paclitaxel, and pembrolizumab followed by second-line carboplatin, pemetrexed, nivolumab, and ipilimumab, the disease progressed rapidly, and the patient died four months after diagnosis. This case illustrates that isolated PIK3CA-mutant NSCLC can be highly refractory to conventional chemoimmunotherapy, including regimens incorporating a cytotoxic T-lymphocyte-associated antigen 4 inhibitor. Further clinical investigation of PI3K-targeted therapies is warranted to establish effective treatment strategies for PIK3CA-mutant NSCLC.