ASCO GU 2018: A Phase III Randomized Study Comparing Perioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy

San Francisco, CA ( The anti-PD-1 antibody nivolumab (nivo) improves overall survival (OS) in metastatic treatment refractory RCC and is generally tolerable. In 2017, there is no standard adjuvant therapy proven to increase OS over surgery alone in non-metastatic (M0) disease. Mouse solid tumor models have revealed an OS benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy.

Two ongoing phase 2 studies of perioperative nivo in RCC patients showed preliminary feasibility and safety with no surgical delays/complications. The PROSPER RCC trial will examine if the addition of perioperative nivo to radical or partial nephrectomy can improve clinical outcomes in patients with locally advanced RCC. In this study the authors are implementing a three-pronged, multidisciplinary approach of pre-surgical priming with nivo followed by resection and adjuvant PD-1 blockade with the goal of increasing cure and recurrence-free survival (RFS) rates in M0 RCC.

Figure 1 demonstrates the study design:
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Tumor biopsy prior to randomization is mandatory to ensure RCC diagnosis but will also permit unparalleled correlative science in this global, unblinded, phase 3 National Clinical Trials Network randomized study. 766 patients with clinical stage ≥T2 or any node positive M0 RCC of any histology will be enrolled. The study arm will receive nivo 240mg IV for 2 doses prior to surgery followed by adjuvant dosing for 9 mo (q2 wks x 3 mo followed by q4 wks x 6 mo). The control arm will undergo the current standard of care: surgical resection followed by observation. Pts are stratified by clinical T stage, node positivity, and histology. There is 84.2% power to detect a 14.4% absolute increase in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 yrs (HR 0.70). The study is also powered to detect a significant OS benefit (HR 0.67). Safety, feasibility, and quality of life are key secondary endpoints. Clinical trial information: NCT03055013

Presented by: Lauren Christine Harshman , Boston, MA, USA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA