What are the newer modalities of treatment for bladder cancer?

From the Guidelines

The most effective treatment approach for bladder cancer involves a combination of immunotherapy, targeted therapies, and molecular characterization of tumors, as evident from recent studies 1. Recent advancements in bladder cancer treatment have significantly expanded therapeutic options beyond traditional approaches.

• Immunotherapy has emerged as a revolutionary treatment modality, with checkpoint inhibitors like pembrolizumab (200mg IV every 3 weeks) and atezolizumab (1200mg IV every 3 weeks) showing remarkable efficacy in metastatic urothelial carcinoma, as supported by the Society for Immunotherapy of Cancer consensus statement 1.
• These medications work by blocking PD-1/PD-L1 pathways, allowing the immune system to recognize and attack cancer cells.
• For patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), intravesical nadofaragene firadenovec (a single dose of 3×1011 viral particles/75 mL every 3 months) offers a gene therapy approach that induces local interferon production.
• Targeted therapies have also shown promise, particularly erdafitinib (8mg daily, adjustable to 9mg based on phosphate levels) for FGFR-altered advanced bladder cancer.
• Enfortumab vedotin (1.25 mg/kg IV on days 1,8, and 15 of a 28-day cycle), an antibody-drug conjugate targeting Nectin-4, has demonstrated efficacy in previously treated advanced urothelial carcinoma, as highlighted in the NCCN Guidelines Insights: Bladder Cancer, Version 3.2024 1. These newer modalities are particularly valuable for patients who have failed platinum-based chemotherapy or are cisplatin-ineligible. The molecular characterization of bladder tumors is increasingly important for treatment selection, as it helps identify patients most likely to benefit from specific targeted therapies based on their tumor's genetic profile, as discussed in the clinical evidence for the first-line treatment of advanced urothelial carcinoma 1. Overall, the treatment of bladder cancer is evolving rapidly, with a focus on personalized medicine and improved patient outcomes, as emphasized by the NCCN Guidelines Insights: Bladder Cancer, Version 2.2016 1.

From the FDA Drug Label

KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma: who are not eligible for any platinum-containing chemotherapy, or who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. Cisplatin Injection is indicated as a single agent for patients with transitional cell bladder cancer which is no longer amenable to local treatments, such as surgery and/or radiotherapy.

The newer modalities of treatment for bladder cancers include immunotherapy with pembrolizumab (KEYTRUDA) and chemotherapy with cisplatin.

• Pembrolizumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma, as well as for patients with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) 2.
• Cisplatin is indicated as a single agent for patients with transitional cell bladder cancer that is no longer amenable to local treatments 3. Key words: bladder cancer, pembrolizumab, cisplatin, immunotherapy, chemotherapy.

From the Research

Newer Modalities of Treatment for Bladder Cancers

• The treatment of non-muscle invasive bladder cancer (NMIBC) is evolving, with a focus on novel therapies to address the limitations of current treatments, such as intravesical Bacille Calmette-Guérin (BCG) and chemotherapy 4.
• Pembrolizumab, an anti-programmed cell death (PD)-1 antibody, has been FDA-approved for BCG-unresponsive, high-risk disease, and other checkpoint inhibitors, such as adenovirus-based therapies, are being investigated 4, 5.
• New mechanisms of drug delivery, including delivery with the GemRIS (TAR-200) device and delivery of intravesical chemotherapy at higher temperatures, are also being explored 4.

Immunotherapy for NMIBC

• Immunotherapy has emerged as a promising approach for the treatment of NMIBC, with several novel agents being investigated, including immune checkpoint inhibitors, toll-like receptor agonists, and recombinant viral vectors 5, 6.
• The use of immunotherapy in NMIBC has the potential to reduce the need for radical cystectomy and improve patient outcomes, particularly for those with BCG-unresponsive disease 6.

Current Treatment Strategies and Future Perspectives

• A systematic review of current treatment strategies for BCG-naïve high-risk NMIBC patients found that alternative treatments, including immune checkpoint inhibitors and novel intravesical therapies, are being explored due to the limitations of BCG therapy 7.
• The review highlighted the need for further validation of these alternative therapies, as well as the importance of ongoing clinical trials in determining their role in future clinical practice 7.

Emerging Therapies

• Several emerging therapies are being investigated for the treatment of NMIBC, including viral gene therapies, interleukin-15 superagonists, small molecule inhibitors of indoleamine (2,3)-dioxygenase 1, and vaccines 6.
• These therapies have the potential to provide new treatment options for patients with NMIBC, particularly those with BCG-unresponsive disease, and may help to reduce the need for radical cystectomy 6.