The Effect of Gene Alterations and Tyrosine Kinase Inhibition on Survival and Cause of Death in Patients With Adenocarcinoma of the Lung and Brain Metastases

Purpose Lung cancer remains the most common cause of both cancer mortality and brain metastases (BM). The purpose of this study was to assess the effect of gene alterations and tyrosine kinase inhibition (TKI) on median survival (MS) and cause of death (CoD) in patients with BM from lung adenocarcinoma (L-adeno). Methods A multi-institutional retrospective database of patients with L-adeno and newly diagnosed BM between 2006 and 2014 was created. Demographics, gene alterations, treatment, MS, and CoD were analyzed. The treatment patterns and outcomes were compared with those in prior trials. Results Of 1521 L-adeno patients, 816 (54%) had known alteration status. The gene alteration rates were 29%, 10%, and 26% for EGFR , ALK , and KRAS , respectively. The time from primary diagnosis to BM for EGFR −/+ was 10/15 months ( P =.02) and for ALK −/+ was 10/20 months ( P EGFR and ALK −, EGFR +, ALK + were 14, 23 ( P P EGFR + patients who did/did not receive TKI before BM was 17/30 months ( P EGFR/ALK hazard ratios: 1.06 [ P =.84]/1.60 [ P =.45], respectively). The CoD was nonneurologic in 82% of patients with known CoD. Conclusion EGFR and ALK gene alterations are associated with delayed onset of BM and longer MS relative to patients without these alterations. The CoD was overwhelmingly nonneurologic in patients with known CoD.