Crizotinib Effective for NSCLC Brain Metastases

Crizotinib demonstrated a significantly higher intracranial disease control rate and prolonged progression-free survival as compared with chemotherapy in patients with treated brain metastases, a study published in the Journal of Clinical Oncology has shown.¹

Previous studies have demonstrated that crizotinib, a kinase inhibitor, is effective for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive. In this study, researchers sought to evaluate the intracranial efficacy of first-line crizotinib vs chemotherapy.

For the phase 3 trial, researchers enrolled 343 patients with ALK-positive NSCLC, of which 23% had stable treated brain metastases at baseline. Patients were randomly assigned 1:1 to receive crizotinib 250 mg orally twice daily, or pemetrexed 500 mg/m² IV plus either cisplatin 75 mg/m² or carboplatin AUC 5-6 IV every 3 weeks for no more than 6 cycles.

Researchers assessed intracranial efficacy at baseline and every 6 or 12 weeks in patients with or without known brain metastases, respectively.

Results showed that there was a nonsignificant improvement in intracranial time to progression with crizotinib in the intent-to-treat population of 363 patients (HR, 0.60; P = .069), patients with treated brain metastases (HR, 0.45; P = .063), and patients without brain metastases (HR, 0.69; P = .323).

The authors noted that although the improvement in intracranial time to progression was not statistically significant in either subgroup, sensitivity to detect treatment differences in or between the 2 subgroups was low.

However, researchers observed a significantly higher intracranial disease control rate with crizotinib vs chemotherapy at 12 weeks (85% vs 45%; P < .001) and 24 weeks (56% vs 25%; P = .006) among patients with treated brain metastases.

Researchers found that progression-free survival was also significantly longer crizotinib as compared with chemotherapy in both patients with treated brain metastases (HR, 0.40; P < .001) and those without brain metastases (HR, 0.51; P < .001), as well as patients in the intent-to-treat population (HR, 0.45; P < .001).

Reference

1. Solomon BJ, Cappuzzo F, Felip E, et al. Intracranial efficacy of crizotinib versus chemotherapy in patients with advanced ALK-positive non–small-cell lung cancer: results from PROFILE 1014 [published online ahead of print March 28, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.63.5888.