Combination Approaches With Systemic Immunotherapy Enhance Medical Oncologists’ Role in NMIBC

Although the management of non–muscle invasive bladder cancer (NMIBC) has traditionally followed a urology-led effort, over time, a more multidisciplinary approach has taken hold with medical oncologists playing a greater role. In particular, the emergence of systemic immunotherapy provides new, bladder-sparing options, especially in patients whose cancer does not respond to traditional Bacillus Calmette-Guérin (BCG) therapy.

Shilpa Gupta, MD, presented on the changing treatment landscape in NMIBC during the 43rd Annual Chemotherapy Foundation Symposium® (CFS): Innovative Cancer Therapy for Tomorrow™ conference and emphasized the growing role of the medical oncologist.¹ Gupta is director, genitourinary medical oncology at the Taussig Cancer Institute, and coleader, genitourinary oncology program at Cleveland Clinic in Cleveland, Ohio.

“Emerging studies are combining novel therapies with systemic immunotherapy, especially in high-risk NMIBC,” Gupta said.

The phase 3 CREST trial (NCT04165317) evaluated sasanlimab, a monoclonal antibody, in a 3-arm combination with BCG in patients with high-risk NMIBC.²

Main Findings of CREST

Findings from the trial showed a significant and clinically meaningful benefit for sasanlimab in combination with BCG plus induction (I) and maintenance (M) over BCG-I plus M in prolonging event-free survival (EFS) in patients with BCG-naive high-risk NMIBC, particularly for patients with carcinoma in situ (CIS) or T1 tumors.

“However, overall survival was not improved, and in the prespecified subgroup analysis, it appears that patients who had CIS benefited more,” Gupta said.

In the study, a total of 1055 patients with BCG-naive high-risk NMIBC were randomly assigned to 3 arms: BCG plus I and M (arm A; n = 352); sasanlimab in combination with BCG plus I (arm B; n = 352); or sasanlimab plus BCG plus I and M (arm C; n = 351).

The primary end point was investigator-assessed event-free survival (EFS) for arm A vs arm C. The key secondary end points were EFS (arm B vs arm C) and overall survival.

The median duration of treatment with sasanlimab was 80.3 weeks (range, 4.0-103.9) in arm A and 84.8 weeks (range, 4.0-104.4) in arm B. In arm A, 46.3% of patients completed sasanlimab treatment at 25 cycles. In arm B, this completion rate was 45.7%.

The most frequent reasons for BCG maintenance discontinuation were adverse events (AEs) in arm A (21.9%) and lack of efficacy in arm C (15.4%).

ESMO Congress 2025

Turning to recent medical conferences, Gupta highlighted the POTOMAC trial (NCT03528694), a phase 3 open-label study that evaluated durvalumab (Imfinzi) in combination with BCG for BCG-naive high-risk NMIBC that was presented at the European Society for Medical Oncology (ESMO) Congress 2025.³

Investigators demonstrated that durvalumab in combination with BCG resulted in a statistically significant and clinically meaningful improvement in disease-free survival (DFS) vs BCG alone at a median follow-up of 5 years. Patients in the experimental arm showed a 32% reduction in risk of DFS (HR, 0.68; 95% CI, 0.50-0.93; P = .015).

“Similar to CREST, event-free survival [EFS] was improved, but overall survival was not. We did not see additional benefit in patients with CIS,” Gupta said.

The experimental treatment had a tolerable and manageable safety profile that was consistent with the known safety profiles of the individual agents.

ALBAN Trial

Another trial in this setting, the ALBAN trial (NCT03799835)⁴ evaluated atezolizumab (Tecentriq) in combination with intravesical BCG compared with BCG alone in BCG-naive patients with high-risk NMIBC. The primary objective was to evaluate the efficacy of atezolizumab combined with BCG, as measured by EFS. The trial did not meet its primary end point of EFS.

“Investigators did not see a benefit in EFS from the addition of atezolizumab to 1 year of BCG therapy,” Gupta said. Positive EFS had been reported with another PD-(L)1 agent, suggesting that any benefit from checkpoint inhibitor therapy plus BCG may be context- and agent-specific rather than a class effect.⁴

“We expect the field to move forward, with durvalumab and sasanlimab approaching regulatory review in this setting, which will give medical oncologists a greater role in the multidisciplinary management of this disease,” Gupta concluded.

REFERENCES

1. Gupta S. Changing treatment landscape for non–muscle-invasive bladder cancer. Presented at: 43rd Annual CFS: Innovative Cancer Therapy for Tomorrow. November 12-14, 2025. New York, NY.

2. Shore ND, Powles TB, 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(8):2806-2814. doi:10.1038/s41591-025-03738-z

3. De Santis M, Edorta JP, Nishiyama H, et al. Durvalumab (D) in combination with Bacillus Calmette-Guérin (BCG) for BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC): final analysis of the phase 3, open-label, randomised POTOMAC trial. Presented at: ESMO Congress 2025. October 17-21, 2025; Berlin, Germany.

4. Roupret M, Bertaut A, Pignot G, et al. ALBAN (GETUG-AFU 37): a phase III, randomized, open-label international trial of intravenous atezolizumab and intravesical Bacillus Calmette-Guérin (BCG) versus BCG alone in BCG-naive high-risk, non-muscle-invasive bladder cancer (NMIBC). Ann Oncol. Published online October 17, 2025. doi:10.1016/j.annonc.2025.09.017