Immunotherapy for bladder cancer

Immunotherapy has transformed the way bladder cancer is treated, opening up new opportunities for patients, especially those with advanced or resistant disease. Through the power of the immune system to attack and destroy cancer cells, immunotherapy gives hope in addition to the conventional treatments such as surgery and chemotherapy.

Immunotherapy utilizes the immune system of the body to recognize and kill cancer cells. In bladder cancer, it has become central, particularly for advanced disease or in cases that are not responsive to standard treatments. The main types of immunotherapy for bladder cancer are immune checkpoint inhibitors and intravesical therapy such as Bacillus Calmette-Guérin (BCG).

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors are drugs that act on proteins like PD-1 or PD-L1, which are used by cancer cells to hide from the immune system. By blocking these checkpoints, the treatment restores T-cells to be able to recognize and kill cancer cells more efficiently. Some of the most prominent checkpoint inhibitors employed in bladder cancer therapy are:

Pembrolizumab (Keytruda): Approved for advanced or metastatic bladder cancer, pembrolizumab has demonstrated significant efficacy. Clinical studies have shown that patients receiving pembrolizumab experienced improved survival rates compared to traditional chemotherapy.

Nivolumab (Opdivo): Another checkpoint inhibitor targeting the PD-1 protein, nivolumab has shown durable responses in patients with advanced urothelial carcinoma who have progressed after standard treatments.

Atezolizumab (Tecentriq): This PD-L1 inhibitor has been utilized in bladder cancer treatment, offering an alternative for patients who may not respond to other therapies.

Bacillus Calmette-Guérin (BCG) Therapy

BCG treatment is done by directly injecting a live, weakened form of Mycobacterium bovis into the bladder. It induces an immune response that occurs in a local site, bringing immune cells to the lining of the bladder to kill cancer cells. BCG continues to be an established treatment for NMIBC, especially in high-risk cases.

Recent advancements in gene therapy have seen novel treatments for bladder cancer. Nadofaragene firadenovec (Adstiladrin) is an example of a non-replicating adenoviral vector-based gene therapy that has been approved for the treatment of high-risk BCG-unresponsive NMIBC. It transfects the gene for interferon alfa-2b into the bladder, eliciting a local immune response against bladder cancer cells. Clinical trials have shown encouraging outcomes with a high percentage of patients having a complete response.

The landscape of bladder cancer treatment continues to evolve with ongoing research and clinical trials exploring new immunotherapeutic approaches:

Cretostimogene (CG0070): An experimental oncolytic immunotherapy drug by CG Oncology, cretostimogene has shown promising results in a late-stage study. Among 112 patients with bladder cancer unresponsive to current therapies, 75% experienced complete remission, with many remaining cancer-free beyond two years. Notably, 97% of participants did not have their cancer invade the bladder muscle, and most avoided surgical removal of the bladder. The treatment was well-tolerated with minimal severe side effects. Cretostimogene has received fast track and breakthrough therapy designations from the FDA and could potentially become a significant advance for bladder cancer patients.

Combination Therapies: Studies are investigating the efficacy of combining checkpoint inhibitors with other treatments. For example, adding pembrolizumab to standard treatments for certain cancers has improved survival rates. These advancements highlight the potential of combination therapies in enhancing treatment outcomes for bladder cancer patients.