A real-world study in advanced non-small cell lung cancer with de novo brain metastasis

Brain metastases are the major cause of life-expectancy shortened for patients with lung cancer. The prognostic value of EGFR mutation subtypes and survival benefit of EGFR-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) patients with de novo brain metastasis is still not clear. Here, we present a real-world study nation-wide focusing on the prognostic value of genomic and therapeutic factors in overall survival (OS) of those patients. We enrolled a total of 233 patients diagnosed with advanced NSCLC and de novo BM from multi-medical centers across China. The enrolled patients were divided into 4 groups, including EGFR 19del, EGFR L858R, EGFR wild-type, and EGFR unknown groups. The median OS of patients with EGFR mutations and all patients were 29.0 and 25.0 months, respectively. There was significant difference in OS of patients among EGFR 19del (n=76), EGFR L858R (n=94), EGFR wild-type (n=46) and EGFR unknown (n=17) groups (30.5 vs 27.5 vs 16.0 vs 25.0, P=0.025). Patients treated by icotinib showed better OS than gefitinib and erlotinib (31.0 vs 25.5 vs 26.5, P=0.02). There was a difference in OS of patients received the whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or WBRT+SRS (20.0 vs 31.0 vs 30.0 months, P<0.001), respectively. In multivariate analysis, patients treated with icotinib had superior iPFS benefit than gefitinib and erlotinib (HR=0.86[95%CI (0.74-1.0)], P=0.04). Besides, the histology of non-adenocarcinomas, the number of BM (>3), and extracranial metastases status could have an independent negative impact on the OS of all patients (P<0.001). EGFR mutant NSCLC patients with de novo BM had a better OS than patients with EGFR wild type. Patients treated with icotinib had longer iPFS than gefitinib and erlotinib but not in OS. Non-adenocarcinomas, number of BM (>3) and extracranial metastases were independent negative prognostic factors in iPFS and OS of all patients. Prospective clinical trials are warranted to explore more effective multimodality in this population.