Dr Powles on EFS With Sasanlimab Plus BCG in BCG-Naive, High-Risk NMIBC

"Overall, I think it's fair to say that sasanlimab plus BCG works to prevent events in BCG-naive non–muscle-invasive [bladder] cancer. [Although] there might be some enrichment [in certain subgroups,] it seems to be working in a broader [patient] population as well."

Thomas Powles, MD, MBBS, MRCP, a professor of genitourinary oncology and director of Barts Cancer Centre at St. Bartholomew's Hospital, Queen Mary University of London, expanded on event-free survival data with sasanlimab in combination with BCG in BCG-naive, high-risk non–muscle-invasive bladder cancer, according to subgroup analyses based on disease stage from the phase 3 CREST study (NCT04165317).

The study demonstrated a positive EFS outcome with the sasanlimab regimen in the intention-to-treat (ITT) population. At a median follow-up of 36.3 months, the EFS rate was 82.1% with the combination vs 74.8% with BCG induction plus maintenance, with a HR of 0.68 (95% CI, 0.49-0.94; 1-sided P = .0095), Powles reported. Further analysis explored key subgroups, particularly patients with carcinoma in situ (CIS), where a greater enrichment effect was observed (HR, 0.53; 95% CI, 0.285-0.982), Powles explained. Kaplan-Meier curves demonstrated a clear and sustained separation in the CIS subgroup, although confidence intervals from the ITT population overlapped with those observed in the CIS subgroup, Powles noted.

Additional subgroup analyses including patients with high-grade Ta and T1 disease similarly fell within these confidence intervals, suggesting that the treatment effect may extend beyond a single subgroup, Powles elaborated. However, Powles cautioned that subset analyses carry an inherent risk of false-positive findings, reinforcing the need for careful interpretation.

The analysis also evaluated PD-L1 as a potential biomarker, Powles continued. Notably, PD-L1 expression was lower in the CIS subgroup, limiting its utility in predicting response in this cohort, Powles indicated. Further investigation into PD-L1 as a predictive marker in the ITT population, as well as in CIS, T1, and high-grade Ta subsets, did not demonstrate significant biomarker enrichment, Powles clarified.

Overall, sasanlimab plus BCG demonstrated efficacy in preventing events in BCG-naive, high-risk NMIBC across subgroups. Efforts to identify robust biomarkers of response remain a priority since the treatment carries a 10% to 15% risk of long-term adverse effects, Powles concluded. In the interim, careful risk-benefit consideration is needed, Powles emphasized.