A prospective phase II trial of neoadjuvant nivolumab plus gemcitabine/cisplatin chemotherapy in muscle-invasive urothelial carcinoma of bladder.

Abstract

494 Background: To assess the efficacy and safety of the combination of nivolumab plus gemcitabine/cisplatin in neoadjuvant setting of muscle-invasive urothelial carcinoma of bladder (MIBC). Methods: In this prospective phase II trial (CRIS, KCT0003804), eligible patients had cT2-T4a N0 MIBC, cisplatin-eligible, and to be planned radical cystectomy. Patients received nivolumab 3 mg/kg on days 1 and 15, cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8 and 15. Study treatment was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (<ypT1), disease-free survival (DFS) and safety. Results: Between Sep 2019 and Oct 2020, 51 patients were enrolled. The majority of patients (96%) completed the planned (median, 3; range 1 to 4) cycles of nivolumab plus gemcitabine/cisplatin without significant toxicities. The most commonly observed adverse events included fatigue, nausea and pruritus. Among the 49 patients who completed study treatment, 12 patients refused surgery but were treated with concurrent chemoradiotherapy. Radical cystectomy was performed in 34 (69%) patients. Pathologic results revealed 12 pCR (ypT0, 35%), 4 ypTis, 3 ypTa, 3 ypT1, and 12 ypT2/T3. Preoperative PD-L1 (22C3 TPS>1%) did not correlate with pCR or pathologic downstaging rates. With a median follow-up of 19 months (95% CI, 17 to 20), 12 patients experienced disease recurrence and median DFS was not reached. Conclusions: Neoadjuvant nivolumab plus gemcitabine/cisplatin was feasible and provided meaningful pathologic responses in patients with MIBC. Clinical trial information: KCT0003804.