Effectiveness of crizotinib in a patient with ALK IHC-positive/FISH-negative metastatic lung adenocarcinoma

Area of Science:

• Oncology
• Molecular Diagnostics
• Pharmacology

Background:

• Anaplastic lymphoma kinase (ALK) rearrangements are key drivers in a subset of non-small cell lung cancer (NSCLC).
• Crizotinib is an FDA-approved tyrosine kinase inhibitor targeting ALK rearrangements.
• Accurate diagnostic testing for ALK rearrangements is crucial for treatment selection.

Observation:

• A heavily pretreated patient with metastatic NSCLC was initially assessed as IHC-positive and FISH-negative for ALK.
• The patient's tumor samples underwent repeated molecular analyses.
• Borderline ALK FISH-positivity, defined as 18.5% positive cells, was eventually demonstrated.

Findings:

• Crizotinib demonstrated clinical effectiveness in this heavily pretreated metastatic NSCLC patient.
• The findings highlight the importance of repeated molecular testing in ambiguous cases.
• Borderline ALK FISH-positivity may represent a responsive population to crizotinib therapy.

Implications:

• This case suggests that crizotinib may benefit NSCLC patients with borderline ALK FISH results.
• It underscores the need for careful interpretation and potential repeat testing in ALK diagnostics.
• Further research is warranted to define the role of crizotinib in patients with borderline ALK alterations.