Intracranial Efficacy of Crizotinib for Patients with ALK-Positive Lung Cancer

Up to half of patients with ALK-rearranged non–small-cell lung cancer (NSCLC) will develop brain metastases within 2 years of diagnosis. To evaluate the use of crizotinib in this setting, investigators conducted an industry-supported, single-arm, phase III trial (PROFILE 1014), in which 343 ALK-rearranged NSCLC patients received frontline treatment with oral crizotinib or intravenous platinum-pemetrexed chemotherapy. Patients with stable treated brain metastases were eligible. Intracranial efficacy was assessed with brain imaging every 6 weeks in the 23% of patients with stable treated brain metastases at baseline or every 12 weeks in those without known brain metastases.

Results were as follows:

• A trend toward improvement in intracranial time to progression was seen with crizotinib versus chemotherapy in the intent-to-treat (ITT) population (hazard ratio, 0.60; P=0.069), in those with treated brain metastases at baseline (HR, 0.45; P=0.063).

• Patients with treated brain metastases at baseline had improved intracranial disease control with crizotinib versus chemotherapy at 12 weeks (85% vs. 45%; P<0.001) and at 24 weeks (56% vs. 25%; P=0.006).

• Rates of intracranial disease progression were 27% in patients with treated brain metastases at baseline and 11% in those without treated brain metastases at baseline.

• Extracranial disease was more common than intracranial disease, and it occurred more often in patients receiving chemotherapy than in those receiving crizotinib.

• Disease progression solely in the brain was more common with crizotinib than with chemotherapy in the ITT population (24% vs. 10%), in those with treated brain metastases at baseline (38% vs. 23%), and in those without brain metastases at baseline (19% vs. 6%).