Prostate cancer immunotherapy

ABSTRACT

Introduction

Medical treatment for prostate cancer (PC) targets hormonal pathways used by malignant cells. Research advances aided in gaining knowledge about implicated molecular pathways and opened the way for establishment of new types of therapies by modifying immunological mechanisms. The aim of this review is to present completed and ongoing research projects regarding PC immunotherapy.

Areas covered

A literature search was conducted in PubMed/MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, and https://www.clinicaltrials.gov/ from inception until 07/2021, to identify completed or ongoing Phase III trials regarding several immunotherapies against PC. Studies on vaccine therapies, CTLA-4 inhibitors, PD-1/PD-L1 inhibitors, PARP inhibitors, PSMA-targeted therapies, and tyrosine kinase inhibitors were considered eligible.

Expert opinion

Although many molecules are being tested against PC cells, only sipuleucel-T has gain approval in the USA. The main reason for this delay in establishing immunotherapy as a standard option for managing PC is the heterogeneity and tumor immune microenvironment complexities. Ipilimumab and olaparib were proved to prolong overall survival significantly against placebo, but a lot of research is going on to identify which patients and at what stage of disease will benefit the most before incorporating them in clinical practice. More recent options such as PSMA-targeted treatments are currently evaluated.

Article Highlights

• Intense research performed on immunotherapy for prostate cancer.

• Vaccine therapy with sipuleucel-T, the only approved immunotherapy for prostate cancer.

• Ipilimumab shows survival benefits.

• Olaparib shows survival benefits.

• Findings should be confirmed on further trials to identify target population characteristics and proper disease stage.

• Immunotherapy is not yet a standard due to tumor environment complex interaction between immune system and malignant cells.

KEYWORDS:

• Immunotherapy
• PARP inhibitors
• PD-1/PD-L1 inhibitors
• prostate cancer
• PSMA
• vaccines

Declaration of Interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One of the peer reviewers on this manuscript declares the following disclosures, but posits that this does not impact their ability to perform this peer review: Advisory Board: BMS, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, Astrazeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Immunomedics/Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Infinity Pharmaceuticals; Research Support to Institution: Sanofi, Astrazeneca, Immunomedics/Gilead, QED, Predicine, BMS; Steering committee of studies: BMS, Bavarian Nordic, Seattle Genetics, QED, G1 Therapeutics (all unpaid), and Astrazeneca, EMD Serono, Debiopharm (paid); Data safety monitoring committee.. Mereo; Travel costs: BMS, Astrazeneca; Writing/Editor fees: Uptodate, Editor of Elsevier Practice Update Bladder Cancer Center of Excellence; Speaking fees: Physicians Education Resource (PER), Onclive, Research to Practice, Medscape, Cancer Network, Masters Lecture Series (MLS). Two additional peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.