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. 2020 Feb 20;22(2):267-277.
doi: 10.1093/neuonc/noz155.

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

Suresh K Balasubramanian  1 , Mayur Sharma  1 , Vyshak A Venur  2 , Philipp Schmitt  3 , Rupesh Kotecha  4 , Samuel T Chao  1   4   5 , John H Suh  1   4   5 , Lilyana Angelov  1   4   6 , Alireza M Mohammadi  4   6 , Michael A Vogelbaum  1   4   6 , Gene H Barnett  1   4   6 , Xuefei Jia  7 , Nathan A Pennell  4   8 , Manmeet S Ahluwalia  1   4   8
Affiliations

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

Suresh K Balasubramanian et al. Neuro Oncol. .

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.

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Figures

Fig. 1
Fig. 1
Univariate analysis showing (A, B) PFS and (C, D) OS in the EGFR/ALK+ and WT cohorts, respectively.
Fig. 2
Fig. 2
Multivariate analysis showing (A, B) PFS and (C, D) OS in the EGFR/ALK+ and WT cohorts, respectively, excluding patients with ECM.
Fig. 3
Fig. 3
Multivariate analysis showing (A, B) PFS and (C, D) OS in the EGFR/ALK+ and WT cohorts, respectively, including patients with ECM.
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