Clinical Perspectives

The Future of Immune Checkpoint Inhibitors for Genitourinary Cancers

November 03, 2020

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Five questions with Dr. Roger Li on immune checkpoint inhibitors for genitourinary cancers:

Dr. Roger Li is a genitourinary oncologist whose clinical practice focuses on the surgical treatment of bladder, prostate, and kidney cancers. He offers a variety of treatment options, including open, laparoscopic and robotic-assisted procedures. Dr. Li’s research interest includes the genomic characterization of genitourinary malignancies in attempt to tailor therapy specific to the patient, as well as the development of novel immunotherapeutic strategies in treating early stages of bladder cancer.

Roger Li, MD

What is immune checkpoint inhibitor immunotherapy?

Immune checkpoint inhibitor (ICI) is a type of drug that blocks certain proteins made by some types of immune system cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check and can prevent T cells from killing cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T cells can kill cancer cells better.

What are some advantages of checkpoint inhibitor as it relates to genitourinary cancers?

Genitourinary malignancies, particularly bladder and kidney cancers, have been historically known to be immunogenic and is responsive to immunotherapy. In fact, immunotherapy-based agents have been used to treat these cancers for decades. The efficacy of ICI in these cancers thus did not come as a surprise. Compared to other systemic agents, ICI are better tolerated and can be administered in patients who would otherwise be ineligible for other forms of systemic therapy, such as chemotherapy.

Where are we with the ability to use checkpoint inhibitor for solid tumors, particularly bladder and kidney cancer?

ICI have been approved in the treatment of metastatic bladder and kidney cancers. In addition, pembrolizumab was also recently approved to treat recurrent localized, non-muscle invasive bladder cancer following first line BCG treatment. ICI use is also being actively investigated in the neoadjuvant and adjuvant settings in the treatment of muscle invasive bladder cancer (MIBC), where they are either used prior to surgical removal of the bladder, or afterwards when the pathology indicates aggressive disease.

What are some of checkpoint inhibitor immunotherapy clinical trials currently available?

In the treatment of bladder cancer, we have two novel combination immunotherapy trials recently opening at Moffitt Cancer Center. In the BCG Unresponsive setting (patient with recurrent non-muscle invasive bladder cancer after first line BCG treatment), we are exploring the efficacy of combined pembrolizumab (which has already gained approval) with CG0070 – an oncolytic virus that targets the bladder cancer cells, kills them and releases specific cancer related proteins into the surroundings to promote a cancer-specific immune attack. It remains to be seen whether this combination of the two agents will achieve therapeutic synergy, leading to higher recurrence free survival and more patients able to retain their bladders (as currently the standard of care for BCG-unresponsive bladder cancer is removal of the bladder). MCC20575.

The second is an investigator-initiated trial, using a similar rationale and drug combination to achieve synergy. We are excited about these trials as the oncolytic virus has been demonstrated in the past to be both safe and has potent antitumor effects when used as monotherapy. In addition, compared to systemic agents, the intravesical administration of the oncolytic virotherapy minimizes systemic toxicity and directly targets the antitumor effect within the bladder. MCC20711.

What are you most excited about the future of checkpoint inhibitor?

Although ICI has brought about a fundamental paradigm shift in cancer treatment, most patients do not respond to therapy. At Moffitt, we are blazing a new trail for the identification of potential biomarkers that can help to select patients with inherent immune reactivity and are more likely to respond to ICI. For those who are less likely to respond, we are coupling ICI with other immunogenic agents, such as oncolytic virus, to foster a more robust immune response, leading to added treatment efficacy.