2377P - Interim results from a phase II clinical study of tislelizumab combined with gemcitabine and cisplatin as a bladder-sparing therapy for urine tumor DNA (utDNA) defined clinical complete response (cCR) MIBC patients

Background

In order to precisely select MIBC patients (pts) for bladder preservation, it’s necessary to establish strict standard for cCR. Our study was conducted to evaluate the efficacy of tislelizumab combined with gemcitabine and cisplatin (GC) as a bladder-sparing therapy for utDNA-defined cCR pts.

Methods

The study enrolled pts were cisplatin-eligible with no carcinoma in situ. Firstly, pts received maximal TURBT, then received tislelizumab 200 mg in day 1 (D1), cisplatin 70 mg/m² D2, and gemcitabine 1000 mg/m² D1 and D8 every 3 weeks for 4 cycles. Secondly, pts further received utDNA testing and clinical restaging were performed. Pts who were utDNA-defined cCR (defined as negative for utDNA, normal urine cytology and MRI imaging, plus bladder biopsies≤cTa.) proceeded bladder preservation, while non-utDNA-defined cCR pts underwent radical cystectomy (RC). Finally, all pts received tislelizumab every 3 weeks for 8 cycles followed by surveillance. The primary endpoint was utDNA-defined cCR rate. Secondary endpoints were 1-year bladder intact disease-free survival(BIDFS) rate, OS and safety.

Results

16 MIBC pts enrolled between Jul. 2021 and Sep. 2022 and 14 pts were analyzed (male 85.7%; median age 62(39-75)). cT2=21.4%, cT3=64.3%, cT4a=14.3%, cN0=78.6%, cN1=21.4%. 100% pts received maximal TURBT. The median number of tislelizumab and GC cycles were 4 (4-4) and 4 (3-4), respectively. Median follow up was 13.2 months (7.9-17.1). The utDNA-defined cCR rate was 35.7% (95% CI, 10.7%-60.7%). Non-utDNA-defined cCR pts received RC and all were≥pT1N0M0. The 1-year BIDFS rate and 1-year OS rate for utDNA-defined cCR pts were 100% (95%CI, 100%-100%) and 100% (95%CI, 100%-100%), respectively. Grade 1-2 immune related adverse events, including rash (n=4), ALT/AST increased (n=3), hyperthyroidism (n=1) and hyperglycaemia (n=1).

Conclusions

The interim results demonstrated the utDNA-defined cCR can successfully select MIBC pts for precise bladder-sparing treatment.

Clinical trial identification

ChiCTR2200067146.

Editorial acknowledgement

Legal entity responsible for the study

The Urology Department, The First Affiliated Hospital, Sun Yat-sen University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.