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Determination of the Incidence of Driver Mutations in Patients with NSCLC and Brain Metastases

Agents with CNS activity may have improved outcomes for patients with non-small cell lung cancer and brain metastases at diagnosis
24 Mar 2021
Pathology/Molecular Biology
Non-Small Cell Lung Cancer

The incidence of brain metastasis at diagnosis in patients with non-small cell lung cancer (NSCLC) harbouring driver mutations was high, according to findings presented at the European Lung Cancer Virtual Congress 2021 (25-27 March). However, these patients achieved similar outcomes with treatment as patients without brain metastases.

Sagar Rakshit of the department of Hematology-Oncology, Mayo Clinic in Rochester, MN, USA and co-investigators 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 Kaplan-Meier and difference was assessed using log-rank test.

Brain metastases at diagnosis was most often observed in patients with RET and BRAF mutations

In this cohort of 98 patients, 31% of patients had brain metastases at diagnosis and 7% additional patients developed brain metastases during their disease course.

In the overall cohort, the highest incidence of brain metastases during entire disease course was observed in RET (100%) and EGFR (45%) mutated patients.

However, among those showing brain metastases at diagnosis, patients with RET and BRAF mutated tumours had the highest incidence (100% and 43% respectively). The incidence of brain metastases at diagnosis in other molecular cohorts was 19/53 (36%) in patients with mutated EGFR, 3/14 (21%) with MET, 4/12 (33%) with ALK, and 1/8 (13%) in patients who had ERBB2 mutation. Neither of the 2 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 14% of patients received no local treatment. 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.


Survival curves for patients with (blue) and without brain metastases (red).

© Sagar Rakshit.


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 favourable 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 CNS penetration.

No external funding was disclosed.


38P – Rakshit S, Bansal R, Desai A, et al. Brain metastases in non-small cell lung cancer in era of molecularly driven therapy. European Lung Cancer Virtual Congress 2021 (25-27 March).

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