ESMO 2017: A Phase III, Randomized, Double-Blind, Multicenter Study of Adjuvant Nivolumab vs Placebo in Patients with High-Risk Invasive Urothelial Carcinoma (CheckMate 274)

Madrid, Spain ( Dr. Bajorin and colleagues presented their phase III trial design assessing adjuvant nivolumab vs placebo in patients with high risk invasive urothelial carcinoma. Standard of care for muscle-invasive bladder cancer is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy + pelvic node dissection or cystectomy + pelvic node dissection alone if cisplatin-ineligible.

A subset of patients may undergo radical cystectomy + pelvic node dissection followed by adjuvant cisplatin-based chemotherapy, however many patients are not candidates for adjuvant chemotherapy or are not treated due to lack of proven survival benefit. Urothelial carcinoma of the ureter or renal pelvis is typically managed with nephroureterectomy, but despite surgery ± chemotherapy many patients with invasive urothelial carcinoma are at high risk of recurrence and death. Nivolumab is a programmed death-1 (PD-1) inhibitor that has proven efficacious for metastatic or unresectable urothelial carcinoma progressing despite chemotherapy (CheckMate 032 [1] and CheckMate 275 [2]). Based on these results, the authors are conducting an international phase III study of adjuvant nivolumab vs placebo in patients with invasive urothelial carcinoma originating in bladder, ureter, or renal pelvis following surgical resection.

Trial design: For this trial, patients must have had radical surgical resection ± cisplatin-based neoadjuvant chemotherapy within the past 120 days and be disease-free (by imaging) ≤4 weeks before randomization. Additionally, patients who did not receive cisplatin-based neoadjuvant chemotherapy must be ineligible for or have refused adjuvant cisplatin. Tumor tissue must be provided for biomarker analysis. Key exclusion criteria include (i) patients that had partial cystectomy or partial nephrectomy, (ii) secondary treatment after surgical removal of urothelial carcinoma (eg, cisplatin-based adjuvant chemotherapy), (iii) prior malignancy within three years except those treated with curative intent and in remission, (iv) or any condition requiring systemic treatment with immunosuppressants (eg, corticosteroids) within 2 weeks of treatment. The co-primary endpoints are disease-free survival (defined as the time between date of randomization and date of first recurrence or death) in patients with tumors expressing ≥1% PD-ligand 1 and in all randomized patients. Secondary endpoints include (i) non-urothelial tract recurrence-free survival, (ii) disease specific survival, and (iii) overall survival. The target enrollment for this trial is 640 patients and recruitment began in February 2016. Clinical trial identification: NCT02632409


1. Sharma P, Callahan MK, Bono P, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): A multicentre, open-label, two-stage, multi-arm, phase ½ trial. Lancet Oncol 2016;17(11):1590-1598.

2. Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol 2017;18(3):312-322.

Speaker: Dean F. Bajorin, Memorial Sloan Kettering Cancer Center, New York, United States of America

Co-Authors: M. D. Galsky (New York, United States of America) J. E. Gschwend (Munich, Germany) Y. Tomita (Niigata, Japan) A. Azrilevich (Princeton, United States of America)

F. Witjes (Nijmegen, Netherlands)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain