Recent clinical trials are reshaping the treatment paradigm for both localized and metastatic bladder cancer, with immunotherapy (IO) playing an increasingly central role. Experts, including Petros Grivas, MD, PhD, are discussing the implications of these trials and how they are being integrated into clinical practice.
Adjuvant and Neoadjuvant Immunotherapy in Localized Bladder Cancer
In the setting of localized muscle-invasive bladder cancer, the CheckMate 274 trial, evaluating adjuvant nivolumab (Opdivo), the AMBASSADOR trial of adjuvant pembrolizumab (Keytruda), and the NIAGARA trial of neoadjuvant and adjuvant durvalumab (Imfinzi) are particularly noteworthy. The NIAGARA trial, which combined durvalumab with gemcitabine/cisplatin before surgery followed by adjuvant durvalumab, demonstrated significant event-free survival and overall survival benefits. The FDA granted priority review based on these results, underscoring the potential for practice-changing impact.
"The trial showed significant event-free survival and overall survival benefit. We're waiting to see the regulatory agency's decision about the efficacy and safety data," said Dr. Grivas, highlighting the anticipation surrounding the regulatory decision and the potential shift in clinical practice.
Immunotherapy Combinations in Metastatic Urothelial Carcinoma
For metastatic urothelial carcinoma, the JAVELIN Bladder 100, CheckMate 901, and EV-302 trials have been pivotal. Updated data from the CheckMate 901 trial, which investigated gemcitabine/cisplatin plus nivolumab versus gemcitabine/cisplatin alone, demonstrated improved efficacy with consistent tolerability. The EV-302 trial, combining enfortumab vedotin (Padcev) with pembrolizumab, showed significantly better outcomes compared to platinum-based chemotherapy in previously untreated patients with locally advanced or metastatic disease.
These trials are rapidly being adopted in both community and academic practices, although challenges and opportunities remain in implementing these treatments effectively. The discussions around these trials highlight the dynamic nature of the field and the ongoing efforts to optimize patient care.
Key Trials and Their Impact
- CheckMate 274: Adjuvant nivolumab demonstrated improved outcomes in patients with localized bladder cancer.
- AMBASSADOR: Adjuvant pembrolizumab showed promise in improving disease-free survival.
- NIAGARA: Perioperative durvalumab significantly improved event-free and overall survival.
- JAVELIN Bladder 100: A landmark trial establishing the role of maintenance avelumab in metastatic urothelial carcinoma.
- CheckMate 901: Gemcitabine/cisplatin plus nivolumab improved efficacy with manageable tolerability.
- EV-302: Enfortumab vedotin plus pembrolizumab significantly enhanced outcomes versus chemotherapy.
