Elsevier

Lung Cancer

Volume 88, Issue 1, April 2015, Pages 108-111
Lung Cancer

Early report
Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers

https://doi.org/10.1016/j.lungcan.2015.01.020Get rights and content

Highlights

  • Brain metastases are frequent in ALK rearranged lung cancers.

  • Brain metastases are frequent in EGFR mutated lung cancers.

  • ∼25% of patients at diagnosis and half at 3-years of survival have brain metastases.

Abstract

Introduction

Brain metastases (BM) are common in non-small-cell lung cancer (NSCLC). However, the baseline incidence and evolution of BM over time in oncogene-driven NSCLCs are seldom reported. In this study, we evaluated the frequency of BM in patients with epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged NSCLC.

Methods

The presence of BM, clinicopathologic data, and tumor genotype were retrospectively compiled and analyzed from a cohort of 381 patients.

Results

We identified 86 EGFR-mutated (90.7% with metastatic disease; 85.9% received an EGFR inhibitor) and 23 ALK-rearranged (91.3% with metastatic disease; 85.7% received an ALK inhibitor) NSCLCs. BM were present in 24.4% of EGFR-mutated and 23.8% of ALK-rearranged NSCLCs at the time of diagnosis of advanced disease. This study did not demonstrate a difference in the cumulative incidence of BM over time between the two cohorts (EGFR/ALK cohort competing risk regression [CRR] coefficient of 0.78 [95% CI 0.44–1.39], p = 0.41). In still living patients with advanced EGFR-mutated NSCLC, 34.2% had BM at 1 year, 38.4% at 2 years, 46.7% at 3 years, 48.7% at 4 years, and 52.9% at 5 years. In still living patients with advanced ALK-rearranged NSCLC, 23.8% had BM at 1 year, 45.5% at 2 years, and 58.4% at 3 years.

Conclusions

BM are frequent in advanced EGFR-mutated or ALK-rearranged NSCLCs, with an estimated >45% of patients with CNS involvement by three years of survival with the use of targeted therapies. These data point toward the CNS as an important unmet clinical need in the evolving schema for personalized care in NSCLC.

Introduction

Non-small-cell lung cancer (NSCLC) is the leading cause of brain metastases (BM) [1]. Amongst those with recurrent/advanced NSCLC, BM are a common culprit for cancer-related morbidity and mortality. The incidence of BM in NSCLC has been reported as >20% at diagnosis, with a significant proportion of patients developing BM over the course of their disease [2], [3]. Recent reports also demonstrate an increase in the documented incidence of BM in NSCLC, likely as a consequence of prolonged survival with newer therapies coupled with improvements in neuroimaging modalities [4].

Far less is known about the baseline incidence and subsequent evolution of BM in the subset of patients with oncogene-driven tumors, i.e. epidermal growth factor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged NSCLC [5], [6]. Given the growing emphasis on molecular profiling and use of targeted therapeutics [7], this is a critical population. An improved understanding of the incidence and evolution of BM in these cases is therefore an area of ongoing need.

Herein, we report the baseline and cumulative incidence of BM in patients with EGFR-mutated or ALK-rearranged advanced NSCLC.

Section snippets

Materials and methods

Cohort selection: Patients seen at Beth Israel Deaconess Medical Center (BIDMC) with a diagnosis of NSCLC and whose tumors were genotyped were identified through an ongoing Institutional Review Board-approved study [8], [9], with a data cutoff of December 19, 2012 for patient inclusion and June 24, 2014 for outcomes.

Tumor genotype: EGFR mutation analysis (exons 18–21) was performed using standard sequencing techniques, and ALK rearrangement was analyzed using the Vysis ALK break-apart

Results

Patient and tumor characteristics: The complete cohort comprised 381 patients, with a median age at diagnosis of 65 years. Self-reported racial groups were 75.9% white, 13.1% Asian, 6.5% black, and 4.4% other. 27.8% of patients were never smokers, 54.9% were former smokers, and 17.3% current smokers. At the time of initial entry into the cohort, 73.8% had stage IV/recurrent disease, and 86.1% had adenocarcinoma histology. EGFR and ALK analysis was successful in 94.2% (359/381) and 91.6%

Discussion

We retrospectively evaluated a cohort of patients with EGFR-mutated or ALK-rearranged advanced NSCLC. BM were common, with nearly 25% of patients with BM at initial diagnosis and approximately half of patients with BM by 3 years in the setting of precision therapies. Limitations of this study include its retrospective nature and the lack of a standardized protocol for CNS assessment. Nevertheless, to the best of our knowledge, this is the largest study to assess the baseline incidence and

Conflict of interest

Daniel B. Costa has received consulting fees and honoraria from Pfizer (unrelated to the current work).

Deepa Rangachari; Norihiro Yamaguchi; Paul A. VanderLaan; Erik Folch; Anand Mahadevan; Scott R. Floyd; Erik J. Uhlmann; Eric T. Wong; Suzanne E. Dahlberg and Mark S. Huberman have no conflicts to disclose.

No other conflict of interest is stated.

Acknowledgments

This work was funded in part through a fellowship from the American Society of Clinical Oncology Conquer Cancer Foundation (DBC), an American Cancer Society grant (RSG 11-186 to DBC), a Lung Cancer Foundation of America-International Association for the Study of Lung Cancer grant (to DBC), National Institutes of Health (NIH) grant CA090578 (to DBC), and Gallup Funds from the Thoracic Oncology Program at the Dana-Farber Cancer Institute (to SED).

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