Promising immunotherapy for prostate cancer

ABSTRACT

Introduction: Sipuleucel-T is the only currently approved immunotherapy for the management of prostate cancer. However, other immunotherapy agents have recently shown activity in prostate cancer and are being developed alone or in combination with other agents.

Areas covered: This article provides a review of positive or encouraging clinical trials of agents under development including vaccines, monoclonal antibodies, immune modulators, gene-mediated cytotoxic immunotherapy and chimeric antigen receptor-modified ‘designer’ T cells in patients with prostate cancer.

Expert opinion: Personalized peptide vaccines have been associated with improvements in overall survival in early phase clinical trials of patients with prostate cancer, which may lead to their future adoption into management. While single agent, monoclonal antibody-based immunotherapy trials and PSA-TRICOM’s phase III trial have not demonstrated statistically significant improvements in overall survival, combinations of these agents with complementary agents have demonstrated encouraging activity. To improve the development and targeting of these therapies, agent and patient selection/modification needs to occur in the context of a rational model of the immune system’s interaction with prostate cancer. In addition, some traditional surrogates of efficacy may need to be reconsidered as multiple trials of immunotherapy in prostate cancer have had conflicting results between progression-free survival and overall survival.

KEYWORDS:

• Antigen spreading
• autologous vaccines
• chimeric antigenreceptor-modified ‘designer’ T cells
• DNA vaccines
• gene-mediated cytotoxic immunotherapy
• immunotherapy
• personalized peptide vaccines
• prostate cancer
• sipuleucel-T
• viral-based vaccines

Article highlights

• Sipuleucel-T is the only approved immunotherapy for patients with prostate cancer based on two separate phase III trials demonstrating a benefit in overall survival.

• In a randomized, double-blind, placebo-controlled phase II trial of patients with advanced prostate cancer, PSA-TRICOM was associated with an improvement in overall survival, but the subsequent phase III trial was reported to not meet the primary endpoint..

• In a randomized phase II trial of dexamethasone with or without a personalized peptide vaccine, the vaccine arm was associated with a significant improvement in median overall survival.

• In a phase II trial of patients with mCRPC treated with pembrolizumab and enzalutamide after previous progression on enzalutamide, three of the first ten patients enrolled in the trial experienced rapid PSA reductions to ≤ 0.2 ng/ml.

• A pilot study of a PARP inhibitor and PD-L1 inhibitor in patients with mCRPC on at least second line therapy demonstrated a PSA response in a majority of patients despite these patients not being selected for the presence or absence of a deletion or mutation in DNA-repair genes.

This box summarizes key points contained in the article.

Declaration of Interest

JC Henegan Jr is on a speaker’s bureau for Sanofi while G Sonpavde has received grants via his institution from Boehringer Ingelheim, Bayer Healthcare, Onyx-Amgen and Merck & Co. He is also a consultant for Pfizer Inc, Genentech, Novartis, Argos, Merck & Co., Sanofi, Agensys, Clinical Care Options, AstraZeneca, UpToDate, Biotheranostics, Exelixis, Bristol Myers-Squibb, Janssen Pharmaceuticals, Amgen Inc and Eisai. Finally, they have also received personal feels from the National Comprehensive Cancer Network (NCCN). The authors have no other 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 apart from those disclosed.

Additional information

Funding

The authors are funded by the University of Mississippi Medical Center, the University of Alabama Birmingham and the Dana Farber Cancer Institute.