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October 02, 2018; 91 (14) Article

PD-1 inhibition has only limited clinical benefit in patients with recurrent high-grade glioma

Sylvia C. Kurz, Lais P. Cabrera, David Hastie, Raymond Huang, Prashin Unadkat, Mikael Rinne, Lakshmi Nayak, Eudocia Q. Lee, David A. Reardon, Patrick Y. Wen
First published August 31, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006283
Sylvia C. Kurz
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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Lais P. Cabrera
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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David Hastie
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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Raymond Huang
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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Prashin Unadkat
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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Mikael Rinne
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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Lakshmi Nayak
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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Eudocia Q. Lee
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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David A. Reardon
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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Patrick Y. Wen
From the Laura and Isaac Perlmutter Cancer Center (S.C.K.), Brain Tumor Center, NYU Langone Medical Center, New York; Dana-Farber Cancer Institute (L.P.C., D.H., M.R., L.N., E.Q.L., D.A.R., P.Y.W.), Center for Neuro-Oncology; and Department of Radiology (R.H., P.U.), Brigham and Women's Hospital, Boston, MA.
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Citation
PD-1 inhibition has only limited clinical benefit in patients with recurrent high-grade glioma
Sylvia C. Kurz, Lais P. Cabrera, David Hastie, Raymond Huang, Prashin Unadkat, Mikael Rinne, Lakshmi Nayak, Eudocia Q. Lee, David A. Reardon, Patrick Y. Wen
Neurology Oct 2018, 91 (14) e1355-e1359; DOI: 10.1212/WNL.0000000000006283

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Abstract

Objective To investigate the question of whether salvage therapy with the programmed cell death protein 1 (PD-1)–blocking antibodies nivolumab or pembrolizumab with or without bevacizumab offers clinical or survival benefit in patients with recurrent high-grade gliomas (HGGs).

Methods This was a single-institution retrospective observational study in 31 adult patients who received pembrolizumab (Keytruda) or nivolumab (Opdivo) with or without concurrent bevacizumab for recurrent high-grade glioma.

Results Median progression-free survival (mPFS) from first anti–PD-1 dose was 3.2 months (95% confidence interval [CI] 2.2–4.2), and there was no difference in patients receiving nivolumab (mPFS 3.8 months, 95% CI 1.7–5.8) compared to patients receiving pembrolizumab (mPFS 2.3 months, 95% CI 1.7–2.8, log rank 3.1, p = 0.08). There was also no difference in mPFS if patients had previously received bevacizumab (mPFS 3.2 months, 95% CI 2–4.3) or were bevacizumab naive (mPFS 3.7, 95% CI 0–7.9, log rank 1.3, p = 0.3). The median survival from date of first anti–PD-1 dose was 6.6 months (95% CI 4.2–9.1).

Conclusion Salvage therapy with nivolumab or pembrolizumab with or without bevacizumab does not confer a survival benefit in this heavily pretreated unselected patient population. Until the results of the currently ongoing clinical trials become available, the use of PD-1–blocking antibodies should be considered in selected individuals only.

Classification of evidence This retrospective observational study provides Class IV evidence that for patients with recurrent HGGs, salvage therapy with nivolumab or pembrolizumab does not significantly improve survival.

Glossary

CI=
confidence interval;
HGG=
high-grade glioma;
IDH=
isocitrate dehydrogenase;
MGMT=
O6-methylguanine-DNA-methyltransferase;
mOS=
median overall survival;
mPFS=
median progression-free survival;
PD-1=
programmed cell death protein 1;
WHO=
World Health Organization

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Class of Evidence: NPub.org/coe

  • Received February 2, 2018.
  • Accepted in final form July 2, 2018.
  • © 2018 American Academy of Neurology
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