TY - JOUR
T1 - Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors
AU - Hendriks, Lizza E. L.
AU - Bootsma, Gerben
AU - Mourlanette, Jean
AU - Henon, Clemence
AU - Mezquita, Laura
AU - Ferrara, Roberto
AU - Audigier-Valette, Clarisse
AU - Mazieres, Julien
AU - Lefebvre, Corentin
AU - Duchemann, Boris
AU - Cousin, Sophie
AU - le Pechoux, Cecile
AU - Botticella, Angela
AU - De Ruysscher, Dirk
AU - Dingemans, Anne-Marie C.
AU - Besse, Benjamin
N1 - Funding Information:
L.E.L.H. has received research funding from Roche and Boehringer Ingelheim; has been a member of the advisory board of Boehringer Ingelheim and Bristol-Myers Squibb (BMS), (both institution and self), has received travel/conference reimbursement from Roche and BMS (self); has been part of a mentorship program with key opinion leaders funded by AstraZeneca; has received fees for educational webinars Quadia (self). and reports no conflict of interest related to this work. L.M. has been a member of the speakers' bureau of BMS and a member of the advisory board of Roche diagnostics. C A-V. has been the principal investigator of industry trials (AstraZeneca, Boehringer Ingelheim, BMS, Novartis and Roche) and has been a member of the advisory board of AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Novartis, MSD, Pfizer and Roche and speakers' bureau of AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Novartis, Pfizer and Roche. J.M. has received institutional research funding from Roche, BMS and AstraZeneca; has served consulting/advisory roles for Novartis, Roche/Genentech, Pfizer, BMS, Lilly and ImClone Systems, MSD and AstraZeneca; and has received travel/accommodation fees from Pfizer, Roche and BMS. C.l.P. has been a member of the advisory board of AstraZeneca and reports no conflict of interest related to this work. D.D.R. has been a member of the advisory board of BMS, AstraZeneca, Roche/Genentech, Merck/Pfizer and Celgene; has received research grants from AstraZeneca, BMS and Boehringer Ingelheim. All income from the advisory board and from the research grants went integrally to the institution. A.-M.C.D. has been a member of the advisory board of BMS, MSD, Roche, Eli Lilly, Takeda, Pfizer and Boehringer Ingelheim and has received research grant from BMS (institution). BD has given expert testimony to BMS and Roche (payment to self) and has received travel and accommodation fees from BMS and Roche (payment to self).. ).B.B. has received institutional grants for clinical and translational research from AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, Ipsen, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda and Tiziana Pharma and has no conflict of interest related to this work. G.B., C.H., R.F., C.L. S.C., A.B., and J Mourlanette (JM = Julien Mazieres) have no conflict of interest to declare.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/7
Y1 - 2019/7
N2 - Introduction: Patients with non-small cell lung cancer (NSCLC) experience leptomeningeal metastases (LM) in 3-9% of cases. Because overall survival (OS) and performance status are very poor, they are mostly excluded from clinical trials. Here, we evaluated survival of patients with NSCLC having LM treated with immune checkpoint inhibitors (ICIs).Methods: A prospectively collected list of patients with advanced NSCLC treated with ICIs between November 2012 and July 2018 in 7 European centres was merged. All patients with LM before ICI start were selected, data were retrospectively added and patients were classified according to the National Comprehensive Cancer Network (NCCN) LM prognostic classification (good/poor). Progression-free survival (PFS) and OS on ICIs were evaluated.Results: Nineteen of 1288 (1.5%) patients had LM; 73.7% had synchronous brain metastases; 73.7% had neurological symptoms at the start of ICIs and 52.6% were in the NCCN LM good prognosis group. Programmed death ligand-1 (PD-L1) expression was known for 42.1% of patients (87.5% positive). Median follow-up was 13 months from the start of ICIs, and median (95% confidence interval [CI]) PFS on ICIs was 2.0 (1.8-2.2) months. Six-month PFS rate was 21.0% and was significantly higher in the NCCN good versus poor prognostic group: 40% vs 0% (p = 0.05). Twelve-month PFS rate was 0%. Median (95% CI) OS from the start of ICIs was 3.7 (0.9-6.6) months. Six-month OS rate was 36.8%, and 12-month OS rate was 21.1%; both were not statistically significantly different for the good versus poor NCCN prognostic group (p = 0.40 and p = 0.56, respectively).Conclusion: Some patients with NSCLC having LM do benefit from ICI treatment; specifically, those in the NCCN LM good prognosis group can obtain a long survival. (C) 2019 Elsevier Ltd. All rights reserved.
AB - Introduction: Patients with non-small cell lung cancer (NSCLC) experience leptomeningeal metastases (LM) in 3-9% of cases. Because overall survival (OS) and performance status are very poor, they are mostly excluded from clinical trials. Here, we evaluated survival of patients with NSCLC having LM treated with immune checkpoint inhibitors (ICIs).Methods: A prospectively collected list of patients with advanced NSCLC treated with ICIs between November 2012 and July 2018 in 7 European centres was merged. All patients with LM before ICI start were selected, data were retrospectively added and patients were classified according to the National Comprehensive Cancer Network (NCCN) LM prognostic classification (good/poor). Progression-free survival (PFS) and OS on ICIs were evaluated.Results: Nineteen of 1288 (1.5%) patients had LM; 73.7% had synchronous brain metastases; 73.7% had neurological symptoms at the start of ICIs and 52.6% were in the NCCN LM good prognosis group. Programmed death ligand-1 (PD-L1) expression was known for 42.1% of patients (87.5% positive). Median follow-up was 13 months from the start of ICIs, and median (95% confidence interval [CI]) PFS on ICIs was 2.0 (1.8-2.2) months. Six-month PFS rate was 21.0% and was significantly higher in the NCCN good versus poor prognostic group: 40% vs 0% (p = 0.05). Twelve-month PFS rate was 0%. Median (95% CI) OS from the start of ICIs was 3.7 (0.9-6.6) months. Six-month OS rate was 36.8%, and 12-month OS rate was 21.1%; both were not statistically significantly different for the good versus poor NCCN prognostic group (p = 0.40 and p = 0.56, respectively).Conclusion: Some patients with NSCLC having LM do benefit from ICI treatment; specifically, those in the NCCN LM good prognosis group can obtain a long survival. (C) 2019 Elsevier Ltd. All rights reserved.
KW - NSCLC
KW - Immune checkpoint inhibition
KW - Leptomeningeal metastases
KW - NIVOLUMAB
U2 - 10.1016/j.ejca.2019.05.019
DO - 10.1016/j.ejca.2019.05.019
M3 - Article
C2 - 31203193
SN - 0959-8049
VL - 116
SP - 182
EP - 189
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -