Clinical Trials
New Trial Data Reshaping Patient Selection for Bladder Cancer Maintenance Immunotherapy
New findings from JAVELIN Bladder 100, IMvigor011, and CREST point to better biomarker-driven selection for bladder cancer maintenance immunotherapy.
Key Takeaways
- PD-L1 expression isn’t a sufficient way to evaluate patients who could benefit from maintenance immunotherapy in bladder cancer, but JAVELIN Bladder 100 shed light on where research needed to go to find the answer.
- Research in the last year, including the IMvigor011 trial, CREST and JAVELIN BLADDER 100 analyses provide clues and pathways to who might benefit from maintenance immunotherapy.
- Community practice oncologists now have some selection answers; a ctDNA framework for post-cystectomy patients, a stage-based rationale for sasanlimab combination among BCG-naïve high-risk NMIBC patients, and advanced urothelial carcinoma selection is moving toward multi-parameter profiling.
Oncologists are closer to the field’s most concrete answer to a question that has resisted resolution since avelumab became the standard of care: which patients derive benefit from maintenance immunotherapy?
In the 2021 published biomarker analysis of the phase 3 JAVELIN Bladder 100 trial, researchers concluded that programmed death-ligand 1 (PD-L1) expression alone is an insufficient selection tool, with responses occurring across PD-L1 expression levels and nonresponders found among PD-L1–positive patients.1 However, the multi-parameter biomarker model incorporating genomic alteration, immune responses and tumor growth showed promising predictive utility, according to the study, signaling where the field needed to go.
A few years later, results from the phase III IMvigor011 trial demonstrated that circulating tumor DNA (ctDNA)-guided adjuvant therapy with atezolizumab led to significantly longer disease-free survival—and overall survival compared with placebo—among patients with muscle-invasive bladder cancer.2 The researchers concluded that the data could lead to redefinition of how advanced disease and patient selection for therapy in urothelial carcinoma and may also spare patients with persistent ctDNA-negative status from potentially toxic and costly adjuvant therapy.
In the CREST trial, PD-L1 expression didn’t predict benefit from sasanlimab and Bacillus Calmette–Guérin (BCG), but stage did, with patients having carcinoma in situ (CIS) and T1 experiencing the strongest gains with 36-month event-free survival (EFS) of 82.1% vs 74.8% for BCG alone.3 The induction-only sasanlimab arm did not show significant EFS benefit.
“Sasanlimab in combination with BCG-I+M has the potential to redefine the treatment paradigm and clinical decision-making for patients with BCG-naïve high-risk non–muscle-invasive bladder cancer (NMIBC), particularly for patients with aggressive CIS or T1 tumors,” according to the study.
In a long-term analyses of patient-reported outcomes (PROs) from the JAVELIN Bladder 100 trial, among patients treated with avelumab (any duration or ≥12 months) and a post hoc analysis comparing quality-adjusted time without symptoms or toxicity (Q-TWiST) between arms, researchers concluded that receiving avelumab had preserved health-related quality of life and control of cancer-related symptoms with manageable toxicity.4 An exploratory subgroup analysis of the same study concluded that avelumab first-line maintenance as the recommended treatment for advanced urothelial carcinoma did not progress after platinum-based chemotherapy.5
Given recently published research, community practice oncologists now have some selection answers; a ctDNA framework for post-cystectomy patients, a stage-based rationale for sasanlimab combination among BCG-naïve high-risk NMIBC patients, and advanced urothelial carcinoma selection is moving toward multi-parameter profiling.
References
- Powles T, Sridhar SS, Loriot Y, et al. Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial. Nat Med. 2021;27(12):2200-2211. doi: 10.1038/s41591-021-01579-0
- Powles T, Kann AG, Castellano D, et al. ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer. N Engl J Med. 2025;393:2395-2408. doi: 10.1056/NEJMoa251188
- Shore ND, Powles T, Bedke J, et al. Sasanlimab plus BCG in BCG-naive, high-risk non-muscle invasive bladder cancer: the randomized phase 3 CREST trial. Nat Med. 2025;31 2806-2814. doi:10.1038/s41591-025-03738-z
- Grivas P, Aragon-Ching JB, Bellmunt J, et al. Avelumab first-line maintenance for advanced urothelial carcinoma: long-term analyses of patient-reported outcomes and Q-TWiST from the JAVELIN Bladder 100 trial. Eur Urol Oncol. 2025;8:941-951. doi:10.1016/j.euo.2025.04.004
- Bellmunt J, Powles T, Park SH, et al. Avelumab first-line maintenance for advanced urothelial carcinoma: long-term outcomes in patients with nonvisceral or lymph node-only disease. Eur Urol. 2025;88:331-338. doi:10.1016/j.eururo.2025.05.017
Key Takeaways
- PD-L1 expression isn’t a sufficient way to evaluate patients who could benefit from maintenance immunotherapy in bladder cancer, but JAVELIN Bladder 100 shed light on where research needed to go to find the answer.
- Research in the last year, including the IMvigor011 trial, CREST and JAVELIN BLADDER 100 analyses provide clues and pathways to who might benefit from maintenance immunotherapy.
- Community practice oncologists now have some selection answers; a ctDNA framework for post-cystectomy patients, a stage-based rationale for sasanlimab combination among BCG-naïve high-risk NMIBC patients, and advanced urothelial carcinoma selection is moving toward multi-parameter profiling.
Oncologists are closer to the field’s most concrete answer to a question that has resisted resolution since avelumab became the standard of care: which patients derive benefit from maintenance immunotherapy?
In the 2021 published biomarker analysis of the phase 3 JAVELIN Bladder 100 trial, researchers concluded that programmed death-ligand 1 (PD-L1) expression alone is an insufficient selection tool, with responses occurring across PD-L1 expression levels and nonresponders found among PD-L1–positive patients.1 However, the multi-parameter biomarker model incorporating genomic alteration, immune responses and tumor growth showed promising predictive utility, according to the study, signaling where the field needed to go.
A few years later, results from the phase III IMvigor011 trial demonstrated that circulating tumor DNA (ctDNA)-guided adjuvant therapy with atezolizumab led to significantly longer disease-free survival—and overall survival compared with placebo—among patients with muscle-invasive bladder cancer.2 The researchers concluded that the data could lead to redefinition of how advanced disease and patient selection for therapy in urothelial carcinoma and may also spare patients with persistent ctDNA-negative status from potentially toxic and costly adjuvant therapy.
In the CREST trial, PD-L1 expression didn’t predict benefit from sasanlimab and Bacillus Calmette–Guérin (BCG), but stage did, with patients having carcinoma in situ (CIS) and T1 experiencing the strongest gains with 36-month event-free survival (EFS) of 82.1% vs 74.8% for BCG alone.3 The induction-only sasanlimab arm did not show significant EFS benefit.
“Sasanlimab in combination with BCG-I+M has the potential to redefine the treatment paradigm and clinical decision-making for patients with BCG-naïve high-risk non–muscle-invasive bladder cancer (NMIBC), particularly for patients with aggressive CIS or T1 tumors,” according to the study.
In a long-term analyses of patient-reported outcomes (PROs) from the JAVELIN Bladder 100 trial, among patients treated with avelumab (any duration or ≥12 months) and a post hoc analysis comparing quality-adjusted time without symptoms or toxicity (Q-TWiST) between arms, researchers concluded that receiving avelumab had preserved health-related quality of life and control of cancer-related symptoms with manageable toxicity.4 An exploratory subgroup analysis of the same study concluded that avelumab first-line maintenance as the recommended treatment for advanced urothelial carcinoma did not progress after platinum-based chemotherapy.5
Given recently published research, community practice oncologists now have some selection answers; a ctDNA framework for post-cystectomy patients, a stage-based rationale for sasanlimab combination among BCG-naïve high-risk NMIBC patients, and advanced urothelial carcinoma selection is moving toward multi-parameter profiling.
References
- Powles T, Sridhar SS, Loriot Y, et al. Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial. Nat Med. 2021;27(12):2200-2211. doi: 10.1038/s41591-021-01579-0
- Powles T, Kann AG, Castellano D, et al. ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer. N Engl J Med. 2025;393:2395-2408. doi: 10.1056/NEJMoa251188
- Shore ND, Powles T, Bedke J, et al. Sasanlimab plus BCG in BCG-naive, high-risk non-muscle invasive bladder cancer: the randomized phase 3 CREST trial. Nat Med. 2025;31 2806-2814. doi:10.1038/s41591-025-03738-z
- Grivas P, Aragon-Ching JB, Bellmunt J, et al. Avelumab first-line maintenance for advanced urothelial carcinoma: long-term analyses of patient-reported outcomes and Q-TWiST from the JAVELIN Bladder 100 trial. Eur Urol Oncol. 2025;8:941-951. doi:10.1016/j.euo.2025.04.004
- Bellmunt J, Powles T, Park SH, et al. Avelumab first-line maintenance for advanced urothelial carcinoma: long-term outcomes in patients with nonvisceral or lymph node-only disease. Eur Urol. 2025;88:331-338. doi:10.1016/j.eururo.2025.05.017
