Whole Brain Radiotherapy With and Without Concurrent Erlotinib in NSCLC with Brain Metastases: a multicentre, open-label, randomized, controlled phase 3 Trial.

Background Erlotinib combined with whole brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase 2 single-arm trial of non-small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase 3, randomized trial. Methods NSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n=115) or WBRT combined with erlotinib arms (n=109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by Mini-Mental State Examination (MMSE). Results A total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months versus 9.2 months for WBRT-alone (p=0.601). Median PFS and overall survival (OS) of combination group were 5.3 versus 4.0 months (p=0.825) and 12.9 versus 10.0 months (p=0.545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 versus 12.8 months; p=0.164), PFS (8.8 versus 6.4 months; p=0.702) and OS (17.5 versus 16.9 months; p=0.221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments. Conclusion Concurrent erlotinib with WBRT didn't improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases.