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

Abstract

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.

Keywords: Immunotherapy; anti-CTLA-4; anti-PD-1; cancer; checkpoint inhibitors; combination; nivolumab; pembrolizumab.