According to an end point analysis of the phase 2 HCRN GU 16-257, transurethral resection of bladder tumor (TURBT) followed by gemcitabine-cisplatin plus nivolumab resulted in a substantial subset of patients with muscle-invasive bladder cancer achieving clinical complete response (cCR).

These results were first presented at the 2023 ASCO Genitourinary Symposium.

According to Matt Galsky, MD, Icahn School of Medicine, New York, NY, and coauthors, advancing the treatment paradigm of patients with muscle-invasive bladder cancer has “been complicated by a lack of prospective studies, rigorous approaches to assess and define clinical complete response, and integration of novel therapies.”

This study enrolled 76 cisplatin-eligible patients with cT2N0M0 to cT4aN0M0 urothelial bladder cancer. All patients received 4 cycles of gemcitabine-cisplatin chemotherapy plus nivolumab. Those patients who achieved a cCR were eligible to omit cystectomy with maintenance nivolumab twice a week for 8 weeks, followed by surveillance. Patients who did not achieve cCR were recommended to cystectomy. Coprimary end points included cCR rate (cCR defined as: normal cytology, imaging, and cT0/cTa) and the association between cCR and 2-year outcomes.

With a median follow-up duration of 27 months, the cCR rate was 43%. There was 1 patient who achieved cCR who opted for immediate cystectomy. The 2-year survival rate of patients who achieved a cCR was 100%, compared to 75.8% of patients who did not achieve a cCR. The 2-year metastasis-free survival was 96.6% vs 74.6%, respectively. For patients who achieved a cCR, the 2-year bladder-intact survival was 72.2%.

There was no association found between baseline ERCC2, ATM, FANCC, or RB1 alterations and the composite end point of ypT0 (in the case of immediate cystectomy) or 2-year bladder-intact metastatic-free survival. However, a tumor mutational burden ≥10 mutations/Mb was significantly associated with this end point.

Source:

Galsky MD, Daneshmand S, Lewis SC, et al. Co-primary endpoint analysis of HCRN GU 16-257: Phase 2 trial of gemcitabine, cisplatin, plus nivolumab with selective bladder sparing in patients with muscle-invasive bladder cancer (MIBC). J Clin Oncol. 2023;41(6):suppl_447-447. doi:10.1200/JCO.2023.41.6_suppl.44