The incidence of brain metastasis at diagnosis in patients with non–small cell lung cancer (NSCLC) harboring driver mutations was high, according to findings presented by Rashkit et al at the European Lung Cancer Virtual Congress 2021 (Abstract 38P). However, these patients achieved treatment outcomes similar to those of patients without brain metastases.

Analysis Details

Researchers assessed the incidence of brain metastases in patients with driver mutations and evaluated survival outcomes. They reviewed lung gene panel data from patients treated at Mayo Clinic from August 2015 to June 2020 to identify patients with NSCLC and different driver mutations and collected clinical data by retrospective review of electronic medical records.

The study included 98 patients with recurrent NSCLC or metastatic disease and targetable molecular alterations, excluding KRAS. The most commonly identified alterations were EGFR in 52% of patients, MET in 13.7%, and ALK in 11.7% of the cohort. The survival analysis was done using the Kaplan-Meier method, and difference was assessed using a log-rank test.

Incidence of Metastasis by Mutation

In this cohort of 98 patients, 31% of patients had brain metastases at diagnosis and an additional 7% of patients developed brain metastases during their disease course. In the overall cohort, the highest incidence of brain metastases during the entire disease course was observed in patients with RET (100%) and EGFR (45%) mutations.

However, among those showing brain metastases at diagnosis, patients with RET and BRAF–mutated tumors had the highest incidence (100% and 43%, respectively). The incidence of brain metastases at diagnosis in other molecular cohorts was 19 of 53 (36%) in patients with mutated EGFR, 3 of 14 (21%) with mutated MET, 4 of 12 (33%) with mutated ALK, and 1 of 8 (13%) with mutated ERBB2. Neither of the two patients with ROS mutations showed brain metastases at diagnosis. Survival outcomes were similar between patients with and without brain metastases.

Patients with brain metastases received local treatment that consisted of radiation alone in 63% of patients, surgery plus radiation in 23%, and no local treatment in 14%. Sixty-nine percent of these patients received targeted systemic treatment.

The median survival was 32 months, which was irrespective of the presence or absence of brain metastases. No statistically significant difference in survival was observed between patients with brain metastases compared to patients with no brain metastases.

The investigators noted that patients with NSCLC and driver mutations had a high incidence of brain metastasis at diagnosis. In addition, contrary to historical controls, patients with molecular alterations showed favorable outcomes despite the presence or development of brain metastasis. The authors suggested that these outcomes could be due to the availability of potent active targeted drugs with good central nervous system penetration.

Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.