Successful Treatment of a Resistant Subclone in ALK-Rearranged NSCLC

Area of Science:

• Oncology
• Molecular Biology
• Radiotherapy

Background:

• Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are standard treatment for ALK-rearranged advanced non-small-cell lung cancer (NSCLC).
• Disease progression typically leads to switching to a subsequent ALK TKI.
• Oligoprogression, treating limited metastatic sites, is an alternative approach for specific cases.

Observation:

• A patient on ceritinib therapy for ALK-rearranged NSCLC developed a single progressive lesion.
• The lesion's location precluded biopsy, necessitating alternative diagnostic methods.
• Liquid biopsy identified the ALK G1202R resistance mutation in circulating tumor DNA.

Findings:

• Definitive radiotherapy was administered to the sole progressive lesion.
• Post-radiotherapy, the ALK G1202R mutation was undetectable via liquid biopsy.
• The patient continued ceritinib treatment with no evidence of disease on subsequent imaging and liquid biopsy.

Implications:

• This case suggests that an oligoprogression strategy, combining local therapy with continued systemic treatment, can potentially eradicate resistant clones.
• Successful eradication of the ALK G1202R mutation indicates a potential for durable response in ALK-rearranged NSCLC.
• This approach may offer a valuable alternative to immediate TKI switching in select patients with oligoprogressive disease.