(UroToday.com) The 2025 ASCO annual meeting featured a urothelial carcinoma rapid oral abstract session and a presentation by Dr. Thomas Powles discussing event free survival subgroup analyses based on disease stage from the CREST study assessing sasanlimab in combination with BCG in BCG-naive, high-risk non muscle invasive bladder cancer. Sasanlimab in combination with BCG (induction and maintenance) significantly improved investigator-assessed event-free survival versus BCG (induction and maintenance) and had a manageable safety profile in patients with BCG-naive high-risk non muscle invasive bladder cancer, according to the primary analysis results from the phase 3 CREST study:
At the 2025 ASCO annual meeting, Dr. Powles and colleagues reported exploratory event-free survival subgroup analyses not previously presented based on disease stage at randomization from Arms A and C.
Eligible patients in CREST were randomized 1:1:1 to receive sasanlimab in combination with BCG (induction and maintenance: Arm A), sasanlimab in combination with BCG (induction: Arm B), or BCG (induction and maintenance: Arm C). To assess the impact on efficacy of CIS and T1 tumors at baseline, post hoc investigator-assessed event-free survival analyses were conducted for the comparison of Arm A versus Arm C. Event-free survival was defined as time from randomization to recurrence of high-grade disease, progression of disease, persistence of CIS (for patients with CIS at randomization), or death due to any cause, whichever occurred first. The trial design for CREST is as follows:
At the data cutoff date (December 2, 2024), the median duration of follow-up for event-free survival was 36.4 and 36.7 months for Arm A and Arm C, respectively. A total of 176 patients with CIS (with or without papillary tumors) were in Arms A and C, 102 of whom had CIS without papillary tumors. A total of 398 patients with T1 tumor were in Arms A and C, 342 of whom had T1 tumor without CIS. For patients with CIS, with or without concomitant papillary tumors, the 3-year event-free survival rate was 83.0% in Arm A and 71.8% in Arm C:
Further disease evolution patterns in patients with CIS for Arms A vs C are as follows:
For patients with T1 tumors, with or without CIS, the 3-year event-free survival rate was 81.3% in Arm A and 72.2% in Arm C:
Further disease evolution patterns in patients with high grade Ta or T1 for Arms A vs C are as follows:
Baseline PD-L1 expression status was not predictive of event free survival benefit, and further research is required to understand the distinct biology that may drive outcomes in high risk non muscle invasive bladder cancer:
A key secondary endpoint was event free survival for arm B versus arm C (HR 1.16, 95% CI 0.87-1.55), demonstrating that BCG maintenance has an important role in the combination regimen across the predefined pathology subgroups:
Dr. Powles concluded his presentation discussing event free survival subgroup analyses based on disease stage from the CREST study assessing sasanlimab in combination with BCG in BCG-naive, high-risk non muscle invasive bladder cancer, with the following take home points:
- Sasanlimab in combination with BCG (induction and maintenance) showed prolonged event free survival compared with BCG (induction and maintenance) in patients with BCG-naïve, high risk non muscle invasive bladder cancer across subgroups, with potential enrichment in certain subgroups
- Patients with CIS appeared to have lower DP-L1 expression versus T1, but this was not predictive of response to sasanlimab + BCG (induction and maintenance)
- BCG maintenance has an important role in the combination regimen across the predefined pathology subgroups
- Monitoring and management of adverse events is a central part of clinical decision making
- Subcutaneous sasanlimab in combination with BCG (induction and maintenance) has the potential to change the treatment paradigm and clinical decision-making for patients with high risk non muscle invasive bladder cancer, particularly for patients with CIS or T1 tumors
Presented by: Thomas Powles, MD, Barts Cancer Centre, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, London, UK
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.