1274P - Leptomeningeal metastases in non-small cell lung cancer patients with an epidermal growth factor receptor mutation

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Justine Kuiper
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors J. Kuiper1, L. Hendriks2, E. Buijs1, J.A. De Langen1, I. Bahce1, E. Thunnissen3, D.A.M. Heideman4, E.J. Speel5, A.C. Dingemans6, E.F. Smit7
  • 1Pulmonary Diseases, VUmc, 1007 MB - Amsterdam/NL
  • 2Pulmonary Diseases, MUMC, 6202 AZ - Maastricht/NL
  • 3Pathology, VU University Medical Center, Amsterdam/NL
  • 4Department Of Pathology, VU University Medical Centre, Amsterdam/NL
  • 5Pathology, Maastricht University Medical Centre, 6229 HX - Maastricht/NL
  • 6Pulmonology, Maastricht University Medical Center (MUMC), NL-6202 AZ - Maastricht/NL
  • 7Dept. Of Pulmonary Diseases, Vrije University Medical Centre (VUMC), NL-1081 HV - Amsterdam/NL



Leptomeningeal metastasis (LM) is considered to be a devastating complication of non-small cell lung cancer (NSCLC). As overall survival (OS) is prolonged in NSCLC patients with an activating epidermal growth factor receptor mutation (EGFR+), especially when treated with targeted therapy, LM may have become more prevalent in this patient group. Currently, there is no standard treatment for EGFR+ NSCLC patients with LM and prognosis is unknown.


The medical records of 229 patients who were diagnosed with EGFR+ NSCLC between July 2002 and January 2014 in 7 hospitals were retrospectively reviewed for diagnosis of LM (by MRI and/or positive cytology of cerebrospinal fluid). Information on symptoms, treatment, progression-free survival (PFS) and OS was collected. OS was estimated by Kaplan-Meier method, differences were determined by log-rank test.


19 patients with LM were identified. Patient characteristics are described in table 1. All but 1 patient had yet progressed on 1st line EGFR TKI-treatment and median PFS on first TKI-treatment was 9.5 months (95% Confidence Interval (CI) 8.0 – 11.0). Median time from diagnosis of advanced-stage NSCLC to diagnosis of LM was 12.3 months (95% CI 7.4 – 17.2). At time of analysis, 4 patients were alive and median time from diagnosis of LM to death or last date of follow-up was 5.7 months (95% CI 0.0 – 14.2). 1-year survival was 26.3%. Median OS of patients who received high dose EGFR-TKI (i.e. 1500 mg erlotinib weekly) after diagnosis of LM (n = 8) was 5.7 months (95% CI 0.0 – 14.8) compared to 4.6 months (95% CI 0.0 – 13.0) in patients (n = 11) who were treated otherwise (P = 0.888).

Patient characteristics Patients (N = 19)
Median age at time of 1st diagnosis of NSCLC Years 48.1 (range 29.2 - 75.2)
No. of patients Percentage (%)
Gender Male 8 42.1
Female 11 57.9
Histology Adenocarcinoma 19 100.0
Performance score PS 0 11 57.9
PS 1 5 26.3
PS 2 3 15.8
Mutation EGFR-exon 18 2 10.5
EGFR-exon 19 14 73.7
EGFR-exon 21 3 15.8
Diagnosis LM MRI 14 73.7
Cytology 1 5.3
MRI + cytology 4 21.1
Treatment at time when LM was diagnosed TKI 11 57.9
Chemo 3 15.8
TKI + chemo 2 10.5
No treatment 3 15.8
Systemic treatment started at time of diagnosis of LM Continuation of TKI 6 31.6
Continuation of TKI + chemo 1 5.3
High-dose TKI 3 15.8
High-dose TKI + chemo 5 26.3
TKI-switch 1 5.3
Start TKI-treatment 2 10.5
No treatment 1 5.3
Radiotherapy started at time of diagnosis of LM WBRT 5 26.3
Radiotherapy (thoracic/lumbal) 3 15.8
None 11* 57.9

* 8 of these patients started high-dose TKI, 1 patient started standard-dose TKI, 1 patient died 5 days after diagnosis of LM and in 1 patient standard-dose TKI was continued. Abbreviations: NSCLC: non-small cell lung cancer. PS: performance score. EGFR: Epidermal growth factor receptor. LM: leptomeningeal metastases. TKI: tyrosine kinase inhibitor. WBRT: whole brain radiotherapy. Chemo: chemotherapy.


Although LM is generally thought to be a fatal complication of NSCLC, in this cohort 26.3% of EGFR+ NSCLC patients was alive 1 year after diagnosis of LM. In this retrospective, multi-center study, there was no statistical significant advantage for patients who received high dose EGFR TKI. Further investigation for optimal treatment of LM in EGFR+ NSCLC patients is warranted.


A.C. Dingemans: Advisory boards for Roche and Astra Zeneca. All other authors have declared no conflicts of interest.