Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors

Lizza E.L. Hendriks; Gerben Bootsma; Jean Mourlanette; Clemence Henon; Laura Mezquita; Roberto Ferrara; Clarisse Audigier-Valette; Julien Mazieres; Corentin Lefebvre; Boris Duchemann; Sophie Cousin; Cecile le Pechoux; Angela Botticella; Dirk De Ruysscher; Anne Marie C. Dingemans; Benjamin Besse

doi:10.1016/j.ejca.2019.05.019

Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors

Lizza E.L. Hendriks^*, Gerben Bootsma^*, Jean Mourlanette^*, Clemence Henon^*, Laura Mezquita^*, Roberto Ferrara^*, Clarisse Audigier-Valette, Julien Mazieres^*, Corentin Lefebvre^*, Boris Duchemann^*, Sophie Cousin^*, Cecile le Pechoux^*, Angela Botticella^*, Dirk De Ruysscher^*, Anne Marie C. Dingemans^*, Benjamin Besse^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

55 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	182-189
Number of pages	8
Journal	European Journal of Cancer
Volume	116
DOIs	https://doi.org/10.1016/j.ejca.2019.05.019
Publication status	Published - Jul 2019
Externally published	Yes

Bibliographical note

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

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10.1016/j.ejca.2019.05.019

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Hendriks, L. E. L., Bootsma, G., Mourlanette, J., Henon, C., Mezquita, L., Ferrara, R., Audigier-Valette, C., Mazieres, J., Lefebvre, C., Duchemann, B., Cousin, S., le Pechoux, C., Botticella, A., De Ruysscher, D., Dingemans, A. M. C., & Besse, B. (2019). Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors. European Journal of Cancer, 116, 182-189. https://doi.org/10.1016/j.ejca.2019.05.019

@article{627588c6ee5740909391b5373c41cbe4,

title = "Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors",

abstract = "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.",

author = "Hendriks, \{Lizza E.L.\} and Gerben Bootsma and Jean Mourlanette and Clemence Henon and Laura Mezquita and Roberto Ferrara and Clarisse Audigier-Valette and Julien Mazieres and Corentin Lefebvre and Boris Duchemann and Sophie Cousin and \{le Pechoux\}, Cecile and Angela Botticella and \{De Ruysscher\}, Dirk and Dingemans, \{Anne Marie C.\} and Benjamin Besse",

note = "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: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = jul,

doi = "10.1016/j.ejca.2019.05.019",

language = "English",

volume = "116",

pages = "182--189",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Ltd.",

}

Hendriks, LEL, Bootsma, G, Mourlanette, J, Henon, C, Mezquita, L, Ferrara, R, Audigier-Valette, C, Mazieres, J, Lefebvre, C, Duchemann, B, Cousin, S, le Pechoux, C, Botticella, A, De Ruysscher, D , Dingemans, AMC & Besse, B 2019, 'Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors', European Journal of Cancer, vol. 116, pp. 182-189. https://doi.org/10.1016/j.ejca.2019.05.019

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.

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.

UR - https://www.scopus.com/pages/publications/85067206280

U2 - 10.1016/j.ejca.2019.05.019

DO - 10.1016/j.ejca.2019.05.019

M3 - Article

C2 - 31203193

AN - SCOPUS:85067206280

SN - 0959-8049

VL - 116

SP - 182

EP - 189

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Survival of patients with non-small cell lung cancer having leptomeningeal metastases treated with immune checkpoint inhibitors

Abstract

Bibliographical note

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