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

59 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Zimmer, L., Apuri, S., Eroglu, Z., Kottschade, L. A., Forschner, A., Gutzmer, R., Schlaak, M., Heinzerling, L., Krackhardt, A. M., Loquai, C., Markovic, S. N., Joseph, R. W., Markey, K., Utikal, J. S., Weishaupt, C., Goldinger, S. M., Sondak, V. K., Zager, J. S., Schadendorf, D., & 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