Bladder Cancer Treatment Advances: What’s the Latest?  | Dana-Farber Cancer Institute

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Bladder cancer treatment is advancing, with several approved immunotherapy options, an approved gene therapy, and an approach to cell therapy planned for testing in clinical trials at Dana-Farber. 

What is bladder cancer? 

The most common form of bladder cancer is urothelial carcinoma, in which the urothelial cells that line the bladder and urinary tract begin to grow out of control and form tumors. 

Learn more about how we diagnose bladder cancer at Dana-Farber. 

How is bladder cancer treated? 

Treatments vary depending on the stage of the cancer. High-grade early-stage bladder cancer is typically treated with immunotherapy and, in some cases, minor surgery, chemotherapy, or radiation. Later-stage invasive cancers have in the past required surgery to remove the bladder, a procedure that substantially reduces quality of life. 

Learn about how we treat bladder cancer at Dana-Farber. 

What new treatments are available for non-invasive bladder cancer? 

Two novel therapies have been recently approved for the treatment of non-muscle invasive bladder cancer. These therapies are approved for use when a patient’s cancer comes back after Bacillus Calmette-Guerin (BCG) treatment, an immunotherapy that introduces a bacterium, BCG, into the bladder to induce an immune response. 

Approved therapies include: 

• A gene therapy called nadofaragene firadenovec (Adstiladrin). This gene therapy is a targeted form of immunotherapy. It does not require hospitalization or special facilities. The therapy introduces a viral vector into the cells that line the bladder. The virus contains genetic instructions that enable cells in the bladder to produce interferon alpha-2b, a substance that stimulates immune activity.  
• An immune therapy called nogapendekin alfa inbakicept (Anktiva). This therapy boosts the activity of another immune stimulating substance called interleukin-15. It is put into the bladder in liquid form and stimulates immune activity. 

These two new therapies are joining another available immune therapy called pembrolizumab. This immunotherapy was already approved for use after a patient’s cancer stops responding to BCG therapy. Pembrolizumab unmasks cancer cells so that the immune system can be more effective at attacking it. 

“A lot of progress has been made with immunotherapy,” says Wenxin (Vincent) Xu, MD, a physician in the Lank Center for Genitourinary Oncology. “More patients are living longer with good disease control with immunotherapy.” 

Another therapy, called cretostimogene, is showing promising results in phase 3 clinical trials. This therapy delivers a cancer-killing virus into cells. 

Other advanced therapies are also on the horizon, and multiple combinations of therapies are being tested in clinical trials. 

“These new therapies are giving patients many exciting alternatives that are safe and don’t dramatically lower quality of life,” says Joaquim Bellmunt, MD, PhD, director of the Bladder Cancer Center in the Lank Center. 

Learn more about bladder cancer clinical trials at Dana-Farber. 

Are there new treatments for invasive bladder cancer? 

Once bladder cancer becomes metastatic, it can become very aggressive, and patients have few options. Dana-Farber researchers want to change that. 

Xu and physician-scientist Rizwan Romee, MD, are investigating the possibility of using natural killer (NK) cell therapy to treat patients with bladder cancer. NK cells are immune cells that occur naturally in the body and patrol for invaders, such as cancer cells. 

Research has shown that patients with higher numbers of NK cells in their bladder tumor tissue do better. So Romee and Xu are developing a clinical trial of a therapy that combines long-lasting NK cells, called cytokine induced memory-like NK cells, with Anktiva, which boosts interleukin-15 and is known to stimulate NK cells. 

“We are exploring novel approaches to immunotherapy to expand the number of patients who experience remission,” says Xu. 

About the Medical Reviewer

Dr Joaquim Bellmunt is presently an Associate Professor at Harvard Medical School and Director of Bladder Cancer Center at Genitourinary Oncology Program of Dana-Farber Cancer Institute. He was the former Director of the Bladder Cancer Center at Beth Israel Deaconess Medical Center. His clinical expertise is in urological diseases, particularly prostate, bladder and kidney cancer. He has extensive experience treating prostate and bladder cancer patients and has been a key investigator in several trials conducted in this patient population.

He has been involved in the development of immunotherapy in bladder cancer since its inception. He has participated on the two phase I trials with atezolizumab (Nature. 2014) and with pembrolizumab (Lancet Oncol. 2017) and the phase II atezolizumab (Lancet 2016) that led to the FDA approval of both agents. Along the same line, he has contributed to the development of these agents in unfit bladder cancer patients (Lancet 2017). One of the most important contributions in bladder cancer have been to be the lead investigator of the phase III randomized study of vinflunine versus BSC and of the pembrolizumab versus chemotherapy that both led to the approval for these agents in the second line. The last trial is a landmark trial showing survival superiority for immunotherapy versus chemotherapy. The results of this last study were published in the NEJM (Bellmunt J, N Engl J Med. 2017). He has also been the PI of the IMvigor 010 study (adjuvant atezolizumab in bladder cancer) that led to the identification of ctDNA utility for MRD monitoring in bladder cancer. He is the co-author of the Javelin 100 study that has led to the recent approval of maintenance avelumab. He is a member of SEOM, SOGUG, ASCO and ESMO.

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