PD-1/PD-L1 pathway inhibitors in advanced prostate cancer

Pedro Isaacsson Velho, Emmanuel S. Antonarakis

Research output: Contribution to journalReview articlepeer-review

Abstract

Introduction: Pharmacological inhibition of immune checkpoint receptors or their ligands represents a transformative breakthrough in the management of multiple cancers. However, immune checkpoint inhibitors have yet to be FDA-approved for the management of metastatic prostate cancer (PCa), the commonest non-cutaneous malignancy in men. Areas covered: We review our current understanding of the PD-1/PD-L1 pathway in cancer, the use of anti-PD-1/PD-L1 therapeutics in PCa, and potential subgroups of PCa patients who may derive the greatest benefit from these agents (such as men with tumors that have expression of PD-L1 and/or high mutational load). We also review the prior and current clinical trials evaluating the blockade of PD-1/PD-L1 in PCa, highlighting some of the key ongoing studies of greatest relevance to the field. Expert commentary: Clinical trials investigating PD-1/PD-L1 inhibitors should be encouraged in patients with PCa. While it is unlikely that immune checkpoint monotherapies will produce long-lasting responses in a substantial proportion of patients, there is early evidence of activity in some patient subsets. These subgroups may include those with high PD-L1 expression, those with hypermutated or microsatellite-unstable tumors, and those enriched for germline and/or somatic DNA-repair gene mutations (e.g. intraductal/ductal histology, primary Gleason pattern 5, and perhaps AR-V7-positive tumors).

Original languageEnglish (US)
Pages (from-to)475-486
Number of pages12
JournalExpert Review of Clinical Pharmacology
Volume11
Issue number5
DOIs
StatePublished - May 4 2018
Externally publishedYes

Bibliographical note

Funding Information:
ES Antonarakis is partially supported by National Institutes of Health grants R01 CA185297 and P30 CA006973, and Department of Defense Prostate Cancer Research Program grants W81XWH-15-2-0050.

Publisher Copyright:
© 2018 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Cancer
  • immunotherapy
  • PD-1
  • PD-L1
  • prostate

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