Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma

Lisa Zimmer, Susmitha Apuri, Zeynep Eroglu, Lisa A. Kottschade, Andrea Forschner, Ralf Gutzmer, Max Schlaak, Lucie Heinzerling, Angela M. Krackhardt, Carmen Loquai, Svetomir Nenad Markovic, Richard W Joseph, Kelly Markey, Jochen S. Utikal, Carsten Weishaupt, Simone M. Goldinger, Vernon K. Sondak, Jonathan S. Zager, Dirk Schadendorf, Nikhil I. Khushalani

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy. Patients and methods A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed. Results In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively. Conclusions Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalEuropean Journal of Cancer
Volume75
DOIs
StatePublished - Apr 1 2017

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Melanoma
Cell Death
Treatment Failure
Therapeutics
ipilimumab
nivolumab
Multicenter Studies
Survival Rate
Retrospective Studies

Keywords

  • Anti-PD-1
  • Disease progression
  • Efficacy
  • Ipilimumab
  • Ipilimumab and nivolumab
  • Melanoma
  • Nivolumab
  • Pembrolizumab
  • Treatment failure

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zimmer, L., Apuri, S., Eroglu, Z., Kottschade, L. A., Forschner, A., Gutzmer, R., ... Khushalani, N. I. (2017). Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. European Journal of Cancer, 75, 47-55. https://doi.org/10.1016/j.ejca.2017.01.009

Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. / Zimmer, Lisa; Apuri, Susmitha; Eroglu, Zeynep; Kottschade, Lisa A.; Forschner, Andrea; Gutzmer, Ralf; Schlaak, Max; Heinzerling, Lucie; Krackhardt, Angela M.; Loquai, Carmen; Markovic, Svetomir Nenad; Joseph, Richard W; Markey, Kelly; Utikal, Jochen S.; Weishaupt, Carsten; Goldinger, Simone M.; Sondak, Vernon K.; Zager, Jonathan S.; Schadendorf, Dirk; Khushalani, Nikhil I.

In: European Journal of Cancer, Vol. 75, 01.04.2017, p. 47-55.

Research output: Contribution to journalArticle

Zimmer, L, Apuri, S, Eroglu, Z, Kottschade, LA, Forschner, A, Gutzmer, R, Schlaak, M, Heinzerling, L, Krackhardt, AM, Loquai, C, Markovic, SN, Joseph, RW, Markey, K, Utikal, JS, Weishaupt, C, Goldinger, SM, Sondak, VK, Zager, JS, Schadendorf, D & Khushalani, NI 2017, 'Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma', European Journal of Cancer, vol. 75, pp. 47-55. https://doi.org/10.1016/j.ejca.2017.01.009
Zimmer, Lisa ; Apuri, Susmitha ; Eroglu, Zeynep ; Kottschade, Lisa A. ; Forschner, Andrea ; Gutzmer, Ralf ; Schlaak, Max ; Heinzerling, Lucie ; Krackhardt, Angela M. ; Loquai, Carmen ; Markovic, Svetomir Nenad ; Joseph, Richard W ; Markey, Kelly ; Utikal, Jochen S. ; Weishaupt, Carsten ; Goldinger, Simone M. ; Sondak, Vernon K. ; Zager, Jonathan S. ; Schadendorf, Dirk ; Khushalani, Nikhil I. / Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. In: European Journal of Cancer. 2017 ; Vol. 75. pp. 47-55.
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abstract = "Background The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-na{\"i}ve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy. Patients and methods A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed. Results In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16{\%} and 21{\%}, respectively. Disease control rate was 42{\%} for the ipi-group and 33{\%} for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54{\%} and 55{\%}, respectively. Conclusions Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-na{\"i}ve patients.",
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T1 - Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma

AU - Zimmer, Lisa

AU - Apuri, Susmitha

AU - Eroglu, Zeynep

AU - Kottschade, Lisa A.

AU - Forschner, Andrea

AU - Gutzmer, Ralf

AU - Schlaak, Max

AU - Heinzerling, Lucie

AU - Krackhardt, Angela M.

AU - Loquai, Carmen

AU - Markovic, Svetomir Nenad

AU - Joseph, Richard W

AU - Markey, Kelly

AU - Utikal, Jochen S.

AU - Weishaupt, Carsten

AU - Goldinger, Simone M.

AU - Sondak, Vernon K.

AU - Zager, Jonathan S.

AU - Schadendorf, Dirk

AU - Khushalani, Nikhil I.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy. Patients and methods A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed. Results In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively. Conclusions Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.

AB - Background The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy. Patients and methods A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed. Results In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively. Conclusions Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.

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KW - Disease progression

KW - Efficacy

KW - Ipilimumab

KW - Ipilimumab and nivolumab

KW - Melanoma

KW - Nivolumab

KW - Pembrolizumab

KW - Treatment failure

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