Sustained Complete Response to Brigatinib in a Young Patient With ALK-Positive NSCLC Harboring I1171N Mutation...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Acquired resistance to ALK tyrosine kinase inhibitors (TKIs) like alectinib is a significant challenge in ALK-rearranged non-small cell lung cancer (NSCLC).
• The ALK I1171N mutation is an emerging mechanism of resistance to second-generation ALK TKIs.

Purpose of the Study:

• To report a case of sustained complete response to brigatinib in a patient with ALK-positive NSCLC who developed resistance to alectinib mediated by the ALK I1171N mutation.
• To highlight the importance of repeat molecular profiling in guiding treatment decisions for advanced NSCLC.

Main Methods:

• Case report of a young, nonsmoker male with metastatic ALK-positive NSCLC.
• Molecular profiling of tumor tissue after disease progression on alectinib.
• Initiation of brigatinib therapy and monitoring of treatment response.

Main Results:

• The patient achieved a complete radiologic response to brigatinib within 3 months of initiation.
• The complete response has been sustained for over 12 months, including durable intracranial disease control.
• The ALK I1171N mutation was identified as the cause of alectinib resistance.

Conclusions:

• Brigatinib can induce a sustained complete response in ALK-positive NSCLC with ALK I1171N-mediated alectinib resistance.
• Repeat molecular testing is essential for identifying resistance mechanisms and optimizing TKI sequencing.
• This case underscores the potential of brigatinib in overcoming specific resistance mutations in ALK-NSCLC.