Patients with non-small cell lung cancer (NSCLC) who develop brain metastases (BM) historically have worse outcomes. In the era of targeted therapy, drugs with CNS activity may have improved outcomes. We aim to evaluate incidence of brain metastases in patients with driver mutations and evaluate survival outcomes.
We collected lung gene panel data at Mayo Clinic between August 2015 and June 2020. We then identified patients with different driver mutations. Clinical data was collected by retrospective review of electronic medical records. Patients with recurrent NSCLC or metastatic disease were included for analysis. Survival analysis was done using Kaplan-Meier and difference was assessed using log-rank test.
We identified a cohort of 98 patients with targetable molecular alterations (excluding KRAS). Most common alterations were EGFR (52%), MET (13.7%), ALK (11.7%). Overall 31% of patients were noted to have BM at diagnosis while 7% additional patients developed BM during their disease course. RET and BRAF mutated patients had the highest incidence of BM at diagnosis (100% and 43% respectively) while overall RET and EGFR mutated patients had highest prevalance of BM (100% and 45% respectively). Local treatment of BM included radiation alone in 63%, surgery plus radiation in 23% and no local treatment in 14%. Targeted treatment was given in 69% of patients. The median survival was 32 months irrespective of presence or absence of BM. No statistically significant difference in survival outcomes was observed between patients with BM at diagnosis/ disease course versus no BM.Table 38P:
Incidence of BM at diagnosis in different mutations
|Gene||BM at diagnosis|
|EGFR (n = 53)||19 (36%)|
|MET (n = 14)||3 (21%)|
|ALK (n = 12)||4 (33%)|
|ERBB2 (n = 8)||1 (13%)|
|BRAF (n = 7)||3 (43%)|
|ROS (n = 2)||0 (0%)|
|RET (n = 2)||2 (100%)|
In the analyzed cohort of patients, we note that patients with NSCLC with driver mutations have a high incidence of BM at diagnosis. Contrary to historical controls, these patients with molecular alterations have favorable outcomes despite development of BM. This could be due to the availability of potent active targeted drugs with good CNS penetration.
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K. Leventakos: Honoraria (institution): Takeda; Honoraria (institution): OncLive; Honoraria (institution): AstraZeneca. All other authors have declared no conflicts of interest.