Entrectinib Response to ROS1-Fusion-Positive Non-Small-Cell Lung Cancer That Progressed on Crizotinib with...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• ROS1 fusions drive 1-2% of non-small cell lung cancer (NSCLC).
• Crizotinib is an ALK/ROS1 tyrosine kinase inhibitor (TKI) effective for ROS1-positive NSCLC.
• Brain metastases can develop despite crizotinib treatment, with ROS1 G2032R being a common resistance mutation.

Observation:

• A 34-year-old patient with ROS1-fusion-positive NSCLC developed crizotinib-resistant brain metastases.
• Chemotherapy stabilized the disease, but leptomeningeal metastasis (LM) occurred.
• Re-challenge with crizotinib failed, but subsequent entrectinib resolved neurological symptoms.

Findings:

• Entrectinib demonstrated efficacy in resolving neurological symptoms associated with central nervous system (CNS) metastases.
• Liquid next-generation sequencing was unable to detect the resistance mechanism due to low circulating tumor DNA (ctDNA).

Implications:

• Sequential entrectinib administration is a potential therapeutic strategy for ROS1-fusion-positive NSCLC with CNS progression during crizotinib therapy.
• This case highlights the importance of considering sequential TKIs for managing advanced NSCLC with brain metastases.
• Further research is needed to elucidate resistance mechanisms and optimize treatment sequencing.