# Exceptional response to brigatinib following alectinib failure in a patient with ALK fusion-positive duodenal carcinoma

## TL;DR

A patient with ALK fusion-positive duodenal carcinoma showed a strong response to brigatinib after alectinib failed, highlighting the potential of ctDNA sequencing to guide treatment.

## Contribution

This is the first report showing brigatinib's efficacy after alectinib failure in ALK fusion-positive duodenal carcinoma.

## Key findings

- Brigatinib led to marked shrinkage of liver metastases after alectinib failure in a patient with ALK fusion-positive duodenal carcinoma.
- Circulating tumor DNA sequencing detected the ALK L1196M mutation, which was sensitive to brigatinib.
- The patient remained on brigatinib for 7 months before tumor progression.

## Abstract

Patients with advanced duodenal carcinoma typically have a poor prognosis due to limited practical chemotherapy options. While studies on genotype-directed therapy in patients with duodenal carcinoma is progressing, clinical data assessing the efficacy of molecularly targeted therapy remains scarce. We report the case of a 65-year-old woman diagnosed with anaplastic lymphocyte kinase (ALK) fusion-positive advanced duodenal carcinoma. The patient had been treated with alectinib for approximately 2 years for ALK-positive duodenal carcinoma but developed progressive liver metastases, indicating alectinib failure. During the disease progression, circulating tumor DNA (ctDNA) sequencing revealed the emergence of ALK L1196M mutation, which demonstrated sensitivity to brigatinib. After switching to brigatinib, marked shrinkage of liver metastases was observed. The patient maintained brigatinib treatment for 7 months until tumor progression. This is the first report demonstrating the efficacy of brigatinib after alectinib failure in a patient with duodenal carcinoma harboring ALK fusion. Furthermore, this case suggests that ctDNA sequencing can detect specific acquired mutations and help expand optimal treatment options for patients.