Selecting immuno-oncology-based drug combinations - what should we be considering?

Lucia Festino, Vito Vanella, Claudia Trojaniello, Paolo A. Ascierto

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION: Checkpoint inhibitor immunotherapy has revolutionized the treatment of many advanced stage cancers. Preexisting immunity is necessary for a response to these agents, which are most effective in inflamed tumors since they principally act by reinforcing preexisting antitumor T-cell responses. An important goal of therapy is to convert the tumor environment from non-inflamed to inflamed in order to facilitate subsequent response to checkpoint inhibitors. Clinical trials are underway to identify checkpoint inhibitor-based combination approaches, which may help to achieve this goal. Areas covered: Anti-PD-1 agents are being assessed in combination with different treatments (e.g. TLR9 agonists, oncolytic peptides, oncolytic vaccines, LAG-3, HDAC inhibitors, GITR, recombinant human interleukin-2) with promising results. PD-1 agents are also being assessed in combination with other locoregional or systemic treatment modalities, including ECT, radiotherapy, chemotherapy, and targeted therapy, with promising results being achieved. Expert commentary: Emerging approaches based on combinations with anti-PD-1 agents seem to offer increased efficacy compared to anti-PD-1 monotherapy. Such combinations also appear to be well tolerated, with safety profiles often comparable to those seen with anti-PD-1 monotherapy. These combination approaches are likely to become an increasing focus of research. There is also the potential for triplet anti-PD-1 combinations.

Original languageEnglish
Pages (from-to)971-985
Number of pages15
JournalExpert Review of Clinical Pharmacology
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

Keywords

  • anti-CTLA-4
  • anti-PD-1
  • cancer
  • checkpoint inhibitors
  • combination
  • Immunotherapy
  • nivolumab
  • pembrolizumab

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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