Immune Checkpoint Blockade in Solid Organ Tumours: choice, dose and predictors of response.
2020
: Immune checkpoint blockade has transformed outcomes across solid organ tumours. Monoclonal antibodies targeting the negative inhibitory CTLA-4 and PD-1/PD-L1 axis can lead to deep and durable responses across a number of tumour streams in the advanced setting. This immunotherapy approach is increasingly used earlier in the treatment paradigm. A rapidly evolving regulatory, reimbursement and drug development landscape has accompanied this novel class of immunotherapy. Unfortunately only a small proportion of patients respond meaningfully to these agents. Here we review how the underlying tumoral genomic, histologic and immunologic characteristics interact within various patient phenotypes, leading to variations in response to checkpoint blockade. Concurrently we outline the clinical trial and real world evidence that allows for appropriate selection of agent, dose and schedule in solid organ malignancies. An exploration of current trends in basic and translational research in immune checkpoint blockade accompanies a commentary on future clinical directions for checkpoint blockade in oncology.
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