Long-lasting response to crizotinib in brain metastases due to EML4-ALK-rearranged non-small-cell lung cancer

Abstract

Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib, an oral ATP-competitive selective inhibitor of ALK. However, crizotinib exhibits extremely poor blood-brain barrier penetration; therefore, it is considered to play a limited role in the treatment of brain metastases. We present a case of a 50-year-old man with a diagnosis of ALK-rearranged NSCLC with brain metastasis and malignant pleural effusion. Despite the several systemic chemotherapy regimens and whole brain radiotherapy, brain metastasis was refractory; therefore, crizotinib was initiated. A CT scan showed a slight reduction in the brain metastasis and no change in intrathoracic disease 17 weeks after initiating crizotinib. Moreover, CT obtained 12 months after crizotinib treatment revealed brain metastasis without progression. To our knowledge, the present case is the second report of crizotinib-responsive brain metastases due to echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)-rearranged NSCLC.

Figure 1

A chest radiograph obtained on admission revealed a massive left pleural effusion and right mediastinal deviation.

Figure 2

CT revealed left lung nodules with pleural effusion, and multiple brain nodules (arrow).

Figure 3

(A) Contrast-enhanced brain CT before initiating crizotinib showing masses with ring enhancement in left frontal lobe and cerebellar hemisphere, and multiple tiny nodules. (B) Contrast-enhanced brain CT obtained on 17 weeks after initiating crizotinib showing all metastatic lesions decreasing in size.