# Sotorasib Is Not Effective in a KRAS‐Mutated Patient With Brain Metastases From Lung Adenocarcinoma due to Multiple Gene Co‐Mutations

## TL;DR

A patient with KRAS-mutated lung cancer did not respond to sotorasib due to multiple co-occurring gene mutations.

## Contribution

This case highlights the importance of comprehensive genomic profiling for treatment selection in driver gene-positive NSCLC.

## Key findings

- Sotorasib was ineffective in a patient with KRAS G12C mutation due to co-mutations in p53 and BRCA2.
- Genomic profiling revealed multiple gene mutations that likely caused resistance to targeted therapy.
- The case emphasizes the need for detailed genetic testing in early-stage NSCLC patients.

## Abstract

A 60‐year‐old man diagnosed with lung adenocarcinoma underwent standard left lower lobectomy. However, he developed brain metastasis 10 months later, and the metastatic lesion was resected surgically. At that time, the KRAS G12C mutation was detected in the metastatic tissue by the Oncomine Dx Target Test. After 16 months, liver metastases appeared, and treatment with sotorasib was initiated. Unexpectedly, however, Sotorasib was ineffective, and the disease progressed. Cancer Genome Profiling (CGP) Test revealed that mutations of p53 and BRCA2 were already present in the patient's primary tumour, resulting in the initial resistance to standard targeted therapy.

We report a case of brain metastasis that occurred during the standard post‐operative treatment for early‐stage NSCLC. Initial multiplex test was performed using the brain metastatic tissue, and the KRAS G12C mutation was detected. However, the response to Sotorasib treatment was not observed. Further genetic testing revealed mutations in multiple driver genes (P53, BRCA2, and KRAS) in the lung cancer cells of our patient at the time of Sotorasib initiation. We present this case as an example of the importance of genomic profiling tests in selecting the appropriate treatment in perioperative patients with driver gene‐positive NSCLC.