ASCO GU 2019: PROSPER: Comparing Perioperative Nivolumab versus Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy

San Francisco, CA (UroToday.com) There is currently no standard adjuvant systemic therapy proven to increase overall survival (OS) over surgery in renal cell carcinoma (RCC). There is controversy over the efficacy of adjuvant targeted therapy given one positive phase 3 study demonstrating a >1 year disease-free survival (DFS) benefit with adjuvant sunitinib in higher risk, clear cell disease (S-TRAC), but 3 other phase 3 studies showing no DFS or OS benefit to 1 year of adjuvant VEGF blockade, with sunitinib (ASSURE), Pazopanib (PROTECT), or Axitinib (ATLAS).

The anti-PD1 antibody nivolumab is an established well tolerated, effective agent in mRCC. Given its favorable tolerability profile and proven ability to increase survival in more advanced disease, nivolumab is a rational option to investigate earlier in the micrometastatic setting, which is characterized by lower disease burden and a potentially more intact immune system.

The trial design is shown in figure 1. This will be a phase 3 open-label randomized study that is not placebo-controlled. The primary endpoint will be recurrence-free survival. Furthermore, the authors will assess safety, tolerability, and quality of life endpoints. There will also be additional correlative science with immunohistochemistry and immunofluorescence analyses, assessment of the impact of inflamed vs. non-inflamed tumor, and assessment of the induction of tumor PD-L1 expression. Whole exome sequencing will be done to identify neoepitope signatures and characterize mutational patterns and frequency. Finally, quality of life will be measured and assessed as well.

Figure 1 – Trial scheme:
UroToday ASCOGU2019 PROSPER RCC

Presented by: Lauren Harshman, MD, ECOG - ACRIN Research group, Assistant Professor, Medicine, Harvard Medical School, Assistant Professor, Medical Oncology, Dana-Farber Cancer Institute, Dana-Farber Cancer Institute

Written By: Gina B. Carithers Founder and Publisher at UroToday.com

Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA