ASCO 2017: A phase III randomized study comparing perioperative nivolumab vs. observation in patients with localized renal cell carcinoma undergoing nephrectomy (PROSPER RCC)

Chicago, IL ( To date, there is no standard adjuvant therapy proven to increase overall survival (OS) over surgery alone in non-metastatic (M0) locally advanced renal cell carcinoma (RCC). The anti-PD-1 antibody nivolumab improves OS in metastatic treatment refractory RCC and is generally tolerable [1]. Two ongoing phase 2 studies of perioperative nivolumab in RCC patients have shown preliminary feasibility and safety with no surgical delays or complications. Dr. Harshman and colleagues presented their trial design of the PROSPER RCC trial, a phase III study comparing perioperative nivolumab vs observation in patients with locally advanced RCC undergoing nephrectomy at today’s ASCO 2017 annual meeting genitourinary cancer poster session.

In this study, tumor biopsy prior to randomization is mandatory to ensure the correct diagnosis and will all unparalleled correlative science in this National Clinical Trials Network study. There will be 766 patients with clinical stage ≥T2 or any node positive M0 RCC of any histology will be enrolled. The study arm will receive nivolumab 240mg IV for 2 doses prior to surgery followed by nivolumab adjuvantly for 9 months (q2 weeks x 3 months followed by q4 weeks x 6 months). The control arm will undergo the current standard of care, surgical resection, followed by observation. Patients will be stratified by T stage, node positivity, and disease histology. The study is designed with 84.2% power to detect a 14.4% absolute increase in the primary endpoint of recurrence-free survival from the ASSURE historical control of 55.8% to 70.2% at 5 yrs (HR 0.70) [2]. Additionally, the study is powered to detect a significant OS benefit (HR 0.67).

The authors conclude that PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the significance of the baseline immune milieu and changes after neoadjuvant priming and to identify predictive gene expression patterns.
Clinical trial: NCT 03055013

Presented By: Lauren Christine Harshman, Dana-Farber Cancer Institute, Boston, MA, USA

Co-Authors: Maneka Puligandla, Naomi B. Haas, Mohamad Allaf, Charles G. Drake, David F. McDermott, Sabina Signoretti, David Cella, Rajan T Gupta, Rupal Satish Bhatt, Eliezer Mendel Van Allen, Toni K. Choueiri, Primo Lara, Anil Kapoor, Daniel Yick Chin Heng, Brian M. Shuch, Michael A.S. Jewett, Daniel J. George, M Dror Michaelson, Michael Anthony Carducci, On Behalf of the PROSPER RCC Investigators

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA

1. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015 Nov 5;373(19):1803-1813.
2. Haas NB, Manola J, Uzzo RB, et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): A double-blind, placebo-controlled, randomized, phase III trial. Lancet 2016 May 14;387(10032):2008-2016.