Tar-200 Plus Anti-PD-1 Therapy Shows Promising Neoadjuvant Activity in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer
New data from the SunRISe-4 trial, recently published in The Lancet Oncology, demonstrate encouraging results for a novel neoadjuvant treatment approach in patients with muscle-invasive urothelial bladder cancer who are unable to receive or choose to avoid cisplatin-based chemotherapy. The trial investigated the combination of TAR-200, an intravesical gemcitabine delivery system, with sacituzumab (sitrulimab), an anti-PD-1 antibody, compared to sacituzumab alone.
the study enrolled patients with clinical stage T2-T4a, N0, M0 bladder cancer and randomized them to receive either four 3-weekly cycles of TAR-200 plus sacituzumab, or sacituzumab monotherapy, prior to radical cystectomy. The primary endpoint was pathologic complete response (pCR), with secondary endpoints including pathologic downstaging and relapse-free survival (RFS).
Results showed a substantially higher pCR rate in the combination arm (38%) compared to the monotherapy arm (24%).Moreover, over 50% of patients treated with TAR-200 plus sacituzumab experienced pathologic downstaging, a result consistent with previously observed data from checkpoint inhibitor therapies.
Early RFS data revealed a 1-year RFS rate of 77% for the combination therapy, compared to 66% with sacituzumab alone – representing a 10% absolute advancement.While the study wasn’t designed to definitively prove statistical significance in RFS, these findings suggest a potential benefit from adding intravesical therapy to anti-PD-1 treatment in the neoadjuvant setting.
The treatment combination demonstrated a manageable safety profile,with no new or unexpected adverse events reported. The majority of grade 3 to 4 adverse events were localized to the urinary tract, manifesting as symptoms or irritation, and were effectively managed by investigators.
