Impact of EGFR mutation and ALK rearrangement on the outcomes of non-small cell lung cancer patients with brain metastasis

Abstract

Background: The impact of activating alterations in non-small cell lung cancer (NSCLC) (epidermal growth factor receptor [EGFR] mutation/anaplastic lymphoma kinase [ALK] translocation) in prognosticating patients with brain metastasis (BM) is not well defined. This study was sought to identify this impact in NSCLC patients with BM accounting for the known validated variables.

Methods: Among 1078 NSCLC-BM patients diagnosed/treated between January 1, 2000 and December 31, 2015, three hundred and forty-eight with known EGFR/ALK status were analyzed. Overall survival (OS) and intracranial progression-free survival (PFS) were measured from the time of BM.

Results: Ninety-one patients had either ALK (n = 23) alterations or EGFR (n = 68) mutation and 257 were wild type (WT; negative actionable mutations/alterations). Median age of EGFR/ALK+ NSCLC BM patients was 60 years (range 29.8-82.6 y) and ~50% (n = 44) had Karnofsky performance status (KPS) score >80. Median number of BM was 2 (1 to ≥99). The median OS for the ALK/EGFR+ NSCLC BM was 19.9 versus 10.1 months for the WT (P = 0.028). The number of BM in the EGFR/ALK+ group did not impact OS (BM = 1 with 21.1 months vs 2-3 with 19.1 months and >3 with 23.7 months, P = 0.74), whereas fewer BM in the WT cohort had significantly better OS (BM = 1 with 13.8 mo, 2-3 with 11.0 mo and >3 with 8.1 mo; P = 0.006) with the adjustment of age, KPS, symptoms from BM and synchronicity.

Conclusions: Number of BM does not impact outcomes in the EGFR/ALK+ NSCLC patients, implying that targeted therapy along with surgery and/or radiation may improve OS irrespective of the number of BM. Number of BM, extracranial metastasis (ECM), and KPS independently affected OS/PFS in WT NSCLC BM, which was consistent with the known literature.

Keywords: ALK; EGFR; NSCLC; actionable mutations; number of brain metastases; radiosurgery; targeted therapy; wild type.