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Erschienen in: Journal of Neuro-Oncology 3/2018

19.05.2018 | Clinical Study

Retrospective study of nivolumab for patients with recurrent high grade gliomas

verfasst von: Megan Mantica, Ashley Pritchard, Frank Lieberman, Jan Drappatz

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2018

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Abstract

Introduction

Patients with recurrent high-grade gliomas (HGG) have limited treatment options. HGG utilize the PD-1 pathway to evade immune responses. Checkpoint inhibitors have demonstrated safety and clinical activity in patients with recurrent glioblastoma. We explored the efficacy of nivolumab in recurrent HGG with a primary objective of progression free survival (PFS) and overall survival (OS).

Methods

We retrospectively analyzed HGG patients treated with nivolumab in our institution. We included patients with advanced HGG who received nivolumab at their oncologist’s decision. Patients received nivolumab 3 mg/kg every 2 weeks until confirmed progression, intolerable toxicity, death, or physician decision. Radiographic assessments were performed every 8 weeks.

Results

Between April 2015 and October 2017, 50 HGG patients received nivolumab. 43 patients received nivolumab with bevacizumab. 44 patients were bevacizumab refractory and 7 patients received nivolumab monotherapy. All had received prior radiation and chemotherapy. 39 adverse events (AEs) were noted [most commonly fatigue (16%) and constipation (10%)]. 4 (8%) patients experienced grade 3–4 AEs. 36 (72%) patients experienced stable disease (SD) at the 2-month assessment. Median duration of SD was 4.3 months (5.1 months in the bevacizumab naïve, 3.8 months in the bevacizumab refractory). Median PFS was 4.3 months (95% CI 3.5–5.3); median OS was 6.5 months (95% CI 6.0–8.8).

Conclusion

Treatment with nivolumab therapy was associated with a manageable safety profile. In a subset of patients, there was disease stabilization in heavily pre-treated recurrent HGG.
Literatur
3.
Zurück zum Zitat Suchorska B, Weller M, Tabatabai G, Senft C, Hau P, Sabel MC, Herrlinger U, Ketter R, Schlegel U, Marosi C, Reifenberger G, Wick W, Tonn JC, Wirsching HG (2016) Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial. Neuro Oncol 18:549–556. https://doi.org/10.1093/neuonc/nov326 CrossRefPubMedPubMedCentral Suchorska B, Weller M, Tabatabai G, Senft C, Hau P, Sabel MC, Herrlinger U, Ketter R, Schlegel U, Marosi C, Reifenberger G, Wick W, Tonn JC, Wirsching HG (2016) Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial. Neuro Oncol 18:549–556. https://​doi.​org/​10.​1093/​neuonc/​nov326 CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Clarke JL, Ennis MM, Yung WK, Chang SM, Wen PY, Cloughesy TF, Deangelis LM, Robins HI, Lieberman FS, Fine HA, Abrey L, Gilbert MR, Mehta M, Kuhn JG, Aldape KD, Lamborn KR, Prados MD, North American Brain Tumor C (2011) Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma? Neuro Oncol 13:1118–1124. https://doi.org/10.1093/neuonc/nor110 CrossRefPubMed Clarke JL, Ennis MM, Yung WK, Chang SM, Wen PY, Cloughesy TF, Deangelis LM, Robins HI, Lieberman FS, Fine HA, Abrey L, Gilbert MR, Mehta M, Kuhn JG, Aldape KD, Lamborn KR, Prados MD, North American Brain Tumor C (2011) Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma? Neuro Oncol 13:1118–1124. https://​doi.​org/​10.​1093/​neuonc/​nor110 CrossRefPubMed
15.
Zurück zum Zitat Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, Brandes AA, Taal W, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Le Rhun E, Dubois F, Weller M, von Deimling A, Golfinopoulos V, Bromberg JC, Platten M, Klein M, van den Bent MJ (2017) Lomustine and Bevacizumab in progressive glioblastoma. N Engl J Med 377:1954–1963. https://doi.org/10.1056/NEJMoa1707358 CrossRefPubMed Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, Brandes AA, Taal W, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Le Rhun E, Dubois F, Weller M, von Deimling A, Golfinopoulos V, Bromberg JC, Platten M, Klein M, van den Bent MJ (2017) Lomustine and Bevacizumab in progressive glioblastoma. N Engl J Med 377:1954–1963. https://​doi.​org/​10.​1056/​NEJMoa1707358 CrossRefPubMed
20.
21.
22.
26.
Zurück zum Zitat Lee EQ, Reardon DA, Schiff D, Drappatz J, Muzikansky A, Grimm SA, Norden AD, Nayak L, Beroukhim R, Rinne ML, Chi AS, Batchelor TT, Hempfling K, McCluskey C, Smith KH, Gaffey SC, Wrigley B, Ligon KL, Raizer JJ, Wen PY (2015) Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma. Neuro Oncol 17:862–867. https://doi.org/10.1093/neuonc/nou350 CrossRefPubMedPubMedCentral Lee EQ, Reardon DA, Schiff D, Drappatz J, Muzikansky A, Grimm SA, Norden AD, Nayak L, Beroukhim R, Rinne ML, Chi AS, Batchelor TT, Hempfling K, McCluskey C, Smith KH, Gaffey SC, Wrigley B, Ligon KL, Raizer JJ, Wen PY (2015) Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma. Neuro Oncol 17:862–867. https://​doi.​org/​10.​1093/​neuonc/​nou350 CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Lassen U, Sorensen M, Gaziel TB, Hasselbalch B, Poulsen HS (2013) Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Anticancer Res 33:1657–1660PubMed Lassen U, Sorensen M, Gaziel TB, Hasselbalch B, Poulsen HS (2013) Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Anticancer Res 33:1657–1660PubMed
28.
Zurück zum Zitat Galanis E, Anderson SK, Lafky JM, Uhm JH, Giannini C, Kumar SK, Kimlinger TK, Northfelt DW, Flynn PJ, Jaeckle KA, Kaufmann TJ, Buckner JC (2013) Phase II study of bevacizumab in combination with sorafenib in recurrent glioblastoma (N0776): a north central cancer treatment group trial. Clin Cancer Res 19:4816–4823. https://doi.org/10.1158/1078-0432.CCR-13-0708 CrossRefPubMed Galanis E, Anderson SK, Lafky JM, Uhm JH, Giannini C, Kumar SK, Kimlinger TK, Northfelt DW, Flynn PJ, Jaeckle KA, Kaufmann TJ, Buckner JC (2013) Phase II study of bevacizumab in combination with sorafenib in recurrent glioblastoma (N0776): a north central cancer treatment group trial. Clin Cancer Res 19:4816–4823. https://​doi.​org/​10.​1158/​1078-0432.​CCR-13-0708 CrossRefPubMed
29.
Zurück zum Zitat Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32:1020–1030. https://doi.org/10.1200/JCO.2013.53.0105 CrossRefPubMedPubMedCentral Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32:1020–1030. https://​doi.​org/​10.​1200/​JCO.​2013.​53.​0105 CrossRefPubMedPubMedCentral
30.
31.
Zurück zum Zitat Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS (2015) Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol 16:257–265. https://doi.org/10.1016/S1470-2045(15)70054-9 CrossRefPubMedPubMedCentral Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS (2015) Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol 16:257–265. https://​doi.​org/​10.​1016/​S1470-2045(15)70054-9 CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Takita M, Matsumura T, Kami M (2006) Cytokine storm and an anti-CD28 monoclonal antibody. N Engl J Med 355:2593 (author reply 2593–2594)PubMed Takita M, Matsumura T, Kami M (2006) Cytokine storm and an anti-CD28 monoclonal antibody. N Engl J Med 355:2593 (author reply 2593–2594)PubMed
35.
Zurück zum Zitat Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319. https://doi.org/10.1056/NEJMoa1411087 CrossRefPubMed Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319. https://​doi.​org/​10.​1056/​NEJMoa1411087 CrossRefPubMed
36.
37.
Zurück zum Zitat Reardon D, Kim T, Frenel J, Santoro A, Lopez J, Subramaniam DS, Siu LL, Rodon J, Tamura K, Saraf S, Morosky A, Stein K, Soria J (2016) ATIM-35. Results of the phase IB Keynote-028 multi-cohort trial of pembrolizumab monotherapy in patients with recurrence PD-L1 positive glioblastoma multiforme (GBM). Neuro Oncol 18:vi25–vi26. https://doi.org/10.1093/neuonc/now212.100 CrossRef Reardon D, Kim T, Frenel J, Santoro A, Lopez J, Subramaniam DS, Siu LL, Rodon J, Tamura K, Saraf S, Morosky A, Stein K, Soria J (2016) ATIM-35. Results of the phase IB Keynote-028 multi-cohort trial of pembrolizumab monotherapy in patients with recurrence PD-L1 positive glioblastoma multiforme (GBM). Neuro Oncol 18:vi25–vi26. https://​doi.​org/​10.​1093/​neuonc/​now212.​100 CrossRef
38.
Zurück zum Zitat Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, Voloschin A, Ramkissoon SH, Ligon KL, Latek R, Zwirtes R, Strauss L, Paliwal P, Harbison CT, Reardon DA, Sampsonc JH (2017) Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase 1 cohorts of CheckMate 143. Neuro Oncol. https://doi.org/10.1093/neuonc/nox208 CrossRefPubMedPubMedCentral Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, Voloschin A, Ramkissoon SH, Ligon KL, Latek R, Zwirtes R, Strauss L, Paliwal P, Harbison CT, Reardon DA, Sampsonc JH (2017) Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase 1 cohorts of CheckMate 143. Neuro Oncol. https://​doi.​org/​10.​1093/​neuonc/​nox208 CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Bouffet E, Larouche V, Campbell BB, Merico D, de Borja R, Aronson M, Durno C, Krueger J, Cabric V, Ramaswamy V, Zhukova N, Mason G, Farah R, Afzal S, Yalon M, Rechavi G, Magimairajan V, Walsh MF, Constantini S, Dvir R, Elhasid R, Reddy A, Osborn M, Sullivan M, Hansford J, Dodgshun A, Klauber-Demore N, Peterson L, Patel S, Lindhorst S, Atkinson J, Cohen Z, Laframboise R, Dirks P, Taylor M, Malkin D, Albrecht S, Dudley RW, Jabado N, Hawkins CE, Shlien A, Tabori U (2016) Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol 34:2206–2211. https://doi.org/10.1200/JCO.2016.66.6552 CrossRefPubMed Bouffet E, Larouche V, Campbell BB, Merico D, de Borja R, Aronson M, Durno C, Krueger J, Cabric V, Ramaswamy V, Zhukova N, Mason G, Farah R, Afzal S, Yalon M, Rechavi G, Magimairajan V, Walsh MF, Constantini S, Dvir R, Elhasid R, Reddy A, Osborn M, Sullivan M, Hansford J, Dodgshun A, Klauber-Demore N, Peterson L, Patel S, Lindhorst S, Atkinson J, Cohen Z, Laframboise R, Dirks P, Taylor M, Malkin D, Albrecht S, Dudley RW, Jabado N, Hawkins CE, Shlien A, Tabori U (2016) Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol 34:2206–2211. https://​doi.​org/​10.​1200/​JCO.​2016.​66.​6552 CrossRefPubMed
43.
Zurück zum Zitat Cloughesy JN, Prados M, Wen PY, Mikkelsen T, Abrey L, Schiff D, Yung WK, Maoxia Z, Dimery I, Friedman HS (2008) A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM). J Clin Oncol 26:2010b–2010b. https://doi.org/10.1200/jco.2008.26.15_suppl.2010b CrossRef Cloughesy JN, Prados M, Wen PY, Mikkelsen T, Abrey L, Schiff D, Yung WK, Maoxia Z, Dimery I, Friedman HS (2008) A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM). J Clin Oncol 26:2010b–2010b. https://​doi.​org/​10.​1200/​jco.​2008.​26.​15_​suppl.​2010b CrossRef
Metadaten
Titel
Retrospective study of nivolumab for patients with recurrent high grade gliomas
verfasst von
Megan Mantica
Ashley Pritchard
Frank Lieberman
Jan Drappatz
Publikationsdatum
19.05.2018
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 3/2018
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-018-2907-4

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