Bevacizumab plus chemotherapy versus chemotherapy in untreated advanced non-squamous non-small-cell lung cancer patients with brain metastases (BAP BRAIN): an open-label, randomized, multicenter, phase III study.

[BACKGROUND] There is a lack of prospective randomized controlled trials of antiangiogenic therapy in patients with brain metastases. We conducted this phase III, randomized, multicenter study (BAP BRAIN) to evaluate the intracranial efficacy and safety of bevacizumab plus chemotherapy in patients with non-squamous non-small-cell lung cancer (NSCLC) and brain metastases, and provide evidence for this previously unexplored subgroup.

[PATIENTS AND METHODS] Treatment-naïve, non-squamous NSCLC patients with confirmed brain metastases and without sensitizing epidermal growth factor receptor or anaplastic lymphoma kinase mutations were screened from 11 centers in China. The eligible patients were randomly assigned (1 : 1) to receive bevacizumab plus pemetrexed-platinum or pemetrexed-platinum for four to six cycles, followed by bevacizumab plus pemetrexed or pemetrexed maintenance until disease progression, unacceptable toxicity, or death. The primary endpoint was intracranial progression-free survival (iPFS), and secondary endpoints included PFS, overall survival (OS), intracranial objective response rate (iORR), systemic ORR, and safety.

[RESULTS] A total of 160 patients were eligible and underwent randomization, and 153 patients received at least one dose of drug and were included in the full analysis set. After a median follow-up of 16.8 months, the median iPFS was 11.07 months in the bevacizumab plus pemetrexed-platinum group versus 7.37 months in the pemetrexed-platinum group [hazard ratio (HR) 0.494, P < 0.001]. Similarly, the median systemic PFS was significantly longer with bevacizumab plus pemetrexed-platinum than with pemetrexed-platinum alone (8.77 months versus 5.23 months, HR 0.540, P < 0.001). The bevacizumab plus pemetrexed-platinum group had better iORR (69.6% versus 32.4%) and ORR (58.2% versus 27.0%) and remission rate of cerebral edema (88.9% versus 41.9%) than the pemetrexed-platinum group. At data cut-off, the median OS was 28.07 months in the bevacizumab plus pemetrexed-platinum group versus 18.53 months in the pemetrexed-platinum group (HR 0.752, P = 0.162). There was no grade ≥3 intracranial hemorrhage, and most of the adverse events were manageable.

[CONCLUSIONS] This study demonstrated encouraging intracranial efficacy and acceptable safety of bevacizumab plus chemotherapy in patients with non-squamous NSCLC and brain metastases in the first-line setting.