From the Guidelines
Immunotherapy is a highly effective treatment option for bladder cancer, and the most recent guidelines recommend its use for patients with non-muscle invasive bladder cancer (NMIBC) and advanced or metastatic disease, as stated in the 2024 NCCN guidelines 1.
Key Recommendations
- For NMIBC, Bacillus Calmette-Guérin (BCG) therapy is the standard immunotherapy approach, typically administered as intravesical instillations once weekly for 6 weeks (induction), followed by maintenance therapy for 1-3 years with 3-week cycles at months 3,6,12,18,24,30, and 36.
- For advanced or metastatic bladder cancer, immune checkpoint inhibitors like pembrolizumab (200mg IV every 3 weeks), nivolumab (240mg IV every 2 weeks), atezolizumab (1200mg IV every 3 weeks), durvalumab, and avelumab have shown efficacy, as reported in the 2020 NCCN guidelines 1.
Mechanism of Action
- Immunotherapy works by enhancing the body's natural immune response against cancer cells, either by stimulating local inflammation (BCG) or by removing the brakes on the immune system (checkpoint inhibitors), allowing T-cells to recognize and attack cancer cells more effectively.
Side Effects and Monitoring
- Common side effects include fatigue, rash, diarrhea, and potential immune-related adverse events affecting various organ systems.
- Regular monitoring of liver and kidney function is essential during treatment, as recommended by the Society for Immunotherapy of Cancer consensus statement 1.
Recent Updates
- The 2024 NCCN guidelines provide updated recommendations for the use of immunotherapy in bladder cancer, including the use of molecular/genomic testing to facilitate treatment decision-making and to prevent delays in administering later lines of therapy 1.
From the Research
Immunotherapy for Bladder Cancer
- Immunotherapy has shown significant promise in the treatment of bladder cancer, with several clinical trials demonstrating its efficacy as a second-line treatment for metastatic urothelial cancer 2, 3, 4.
- The US Food and Drug Administration has approved five drugs for the treatment of metastatic urothelial cancer, including three Programmed cell-death protein 1 (PD-1) inhibitors and two programmed cell-death ligand 1 (PD-L1) inhibitors 2.
- Pembrolizumab, nivolumab, and atezolizumab are PD-1 inhibitors, while durvalumab and avelumab are PD-L1 inhibitors 2.
- Atezolizumab and pembrolizumab are the only Food and Drug Administration-approved checkpoint inhibitors for cisplatin-ineligible patients 2.
- The KEYNOTE-361 clinical trial demonstrated that pembrolizumab plus chemotherapy did not significantly improve efficacy compared to chemotherapy alone as a first-line treatment for advanced urothelial carcinoma 5.
- A cost-effectiveness analysis of pembrolizumab versus carboplatin-based chemotherapy as first-line treatment for PD-L1-positive locally advanced or metastatic urothelial carcinoma ineligible for cisplatin-based therapy found that pembrolizumab was cost-effective 6.
Clinical Trials and Studies
- The KEYNOTE-045, IMvigor211, CheckMate275, Javelin Solid Tumor, MEDI4736, and KEYNOTE-0528 clinical trials have investigated the use of immunotherapy in bladder cancer 2.
- The KEYNOTE-361 clinical trial was a randomized, open-label, phase 3 trial that compared pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma 5.
- A study published in the Journal of Clinical Advances in Hematology & Oncology discussed the recent development of T-cell checkpoint inhibitors in advanced and metastatic urothelial cancer and addressed their potential use in combination 4.
Treatment Options and Efficacy
- Immunotherapy is approved as a second-line treatment for metastatic urothelial cancer, and its use as a first-line agent is limited to patients who are ineligible for cisplatin-based treatments 2.
- Pembrolizumab has been shown to have meaningful, durable, and well-tolerated antitumor activity in patients with advanced or metastatic urothelial carcinoma 6.
- The addition of pembrolizumab to first-line platinum-based chemotherapy did not significantly improve efficacy and should not be widely adopted for treatment of advanced urothelial carcinoma 5.