Researchers analyzing biomarkers from the phase 2 SunRISe-4 Trial found that high tumor mutational burden (TMB), genomic disease burden (GDB), and PD-L1 expression were linked to better pathologic overall response in patients with muscle-invasive bladder cancer (MIBC) receiving cisplatin-free neoadjuvant therapy.
The study evaluated tissue and urine samples from 88 patients treated with a sustained intravesical gemcitabine drug release system (gem-iDRS) plus cetrelimab or cetrelimab alone. Researchers explored whether genomic and immune biomarkers could help identify patients most likely to benefit from treatment.
Patients with high baseline TMB achieved a 41% pathologic overall response rate, while high GDB was associated with a 50% response rate. Elevated PD-L1 expression was also linked to improved response. However, none of the biomarkers predicted pathologic complete response or recurrence-free survival.
The analysis also found that TP53 and ATM gene alterations were significantly more common in patients with high TMB. Researchers noted that the biomarkers appeared biologically distinct, with little overlap between TMB, GDB, and PD-L1 expression.
Investigators concluded that larger prospective studies are needed to determine whether these biomarkers can reliably guide patient selection for cisplatin-free neoadjuvant treatment strategies in MIBC.