Novel immunotherapy combinations for genitourinary cancers

ABSTRACT

Introduction: Several immune checkpoint inhibitors are FDA-approved for metastatic/advanced RCC and urothelial carcinoma (UC) based on improvements in survival. The dendritic cell vaccine, sipuleucel-T, is also approved for patients with mCRPC, based on a 4-month survival benefit.

Areas covered: Preclinical evidence suggests that there is promise in combining immune checkpoint inhibitors with several different classes of anti-cancer agents, including tumor-directed vaccines, cytokines, chemotherapy, and multi-targeted tyrosine kinase inhibitors. Here we review immunotherapy combinations currently approved for RCC, UC, and prostate cancer with a focus on emerging therapies. We conducted a search of peer-reviewed publications and recent meeting abstracts and provide an overview of ongoing combination immunotherapy trials for genitourinary malignancies and discussion of preliminary findings where available.

Expert opinion: Recently, many potential immunotherapy combinations have emerged. In addition to determining clinical activity, important challenges include investigating additive adverse effects and determining the best sequence of therapy.

KEYWORDS:

• Genitourinary oncology
• combination immunotherapy
• checkpoint inhibitor
• therapeutic cancer vaccines

Article highlights

• Immunotherapies approved for genitourinary malignancies include immune checkpoint inhibitor antibodies (metastatic/advanced renal cell carcinoma and urothelial carcinoma), recombinant interleukin-2 (metastatic renal cell carcinoma) and the sipuleucel-t vaccine (metastatic castration-resistant prostate cancer).

• Combining immune checkpoint inhibitors with other agents that have immunomodulatory effects is an active area of clinical investigation for genitourinary malignancies.

• The FDA-approved pembrolizumab (anti-PD-1) plus axitinib and avelumab (anti-PD-L1) plus axitinib for advanced and metastatic renal cell carcinoma in 2019, highlighting the potential for enhanced activity when combining immune checkpoint inhibitors with multi-targeted tyrosine kinase inhibitors (i.e. axitinib).

• Several ongoing clinical studies are testing checkpoint inhibitor plus multi-targeted tyrosine kinase inhibitors in metastatic/advanced urothelial carcinoma, with preliminary reports showing promising activity.

• Immune checkpoint inhibitors appear to have minimal activity in prostate cancer. Therefore, testing combinations of immune checkpoint inhibitors with tumor targeted vaccine and cytokines is also an active area of clinical investigation.

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Declaration of interest

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

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.