Targeted therapy for patients with ALK-positive NSCLC and brain metastases

This study aimed to test whether the ALK inhibitor drug crizotinib (Xalkori) was more effective than chemotherapy at treating ALK-positive NSCLC that has spread to the brain. The authors concluded that crizotinib is more beneficial for this patient group than chemotherapy.

Several non-small-cell lung cancers (NSCLCs) are driven by a process called ALK-gene-rearrangement, which involves the anaplastic lymphoma kinase (ALK) gene joining with another gene. In patients with ALK-positive NSCLC, metastasis (cancer spread) to the brain is common. Certain drugs, including crizotinib, target ALK-positive NSCLCs and might be effective at treating ALK-positive NSCLC that has spread to the brain. It is not clear whether treatment with crizotinib is more effective than chemotherapy in these patients.

343 patients with advanced ALK-positive NSCLC were included. 172 patients were treated with crizotinib (group 1) while 171 patients were treated with chemotherapy (group 2). Of these 343 patients, 79 had brain metastases (BM) at the start of the trial and 263 did not.

The time from the start of the trial until new or worsening brain lesions was not significantly different for group 1 patients with BM (average 15.7 months) compared to group 2 patients (12.5 months).

Overall, intracranial disease control rate (IC-DCR, patients with a complete response to treatment) at 24 weeks for patients in group 1 was 56%. IC-DCR for patients in group 2 was 25%.

Average progression free survival (PFS – time from beginning of trial until disease progression) for group 1 patients with BM was 9 months compared to 4 months for group 2 patients. In patients without BM, PFS was an average of 11.1 months for group 1 patients and 7.2 months for group 2 patients.

The authors concluded that for patients with brain metastases, crizotinib is more effective than chemotherapy.

This study was funded by Pfizer, the manufacturers of crizotinib.