Clinical Trial Protocol

The future of perioperative therapy in advanced renal cell carcinoma: how can we PROSPER?

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

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Maneka Puligandla

Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

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Brian M Shuch

Department of Urology, Yale School of Medicine, New Haven, CT, USA

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Bradley C Leibovich

Department of Urology, Mayo Clinic, Rochester, MN, USA

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Anil Kapoor

Division of Urology, McMaster University, Hamilton, ON, Canada

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Viraj A Master

Department of Urology, Emory University School of Medicine, Atlanta, GA, USA

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Charles G Drake

Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA

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Daniel YC Heng

Tom Baker Cancer Center, Calgary, AB, Canada

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Primo N Lara

Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA, USA

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Toni K Choueiri

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

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Deborah Maskens

Kidney Cancer Canada, Toronto, Ontario, Canada

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Eric A Singer

Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

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Scott E Eggener

Section of Urology, University of Chicago, Chicago, IL, USA

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Robert S Svatek

Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

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Walter M Stadler

Department of Medicine (Hematology/Oncology), University of Chicago, Chicago, IL, USA

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Suzanne Cole

Department of Medicine (Hematology/Oncology), University of Texas Southwestern Medical Center, Dallas, TX, USA

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Sabina Signoretti

Department of Pathology, Brigham & Women's Hospital, Boston, MA, USA

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Rajan T Gupta

Departments of Radiology & Surgery & The Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

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Marc Dror Michaelson

Massachusetts General Hospital Cancer Center, Boston, MA, USA

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David F McDermott

Division of Hematology-Oncology & Cancer Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

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David Cella

Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

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Lynne I Wagner

Department of Social Sciences & Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA

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Naomi B Haas

Division of Hematology/Oncology, Abramson Cancer Center, University of Pennsylvania, PA, USA

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Michael A Carducci

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

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Lauren C Harshman

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

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Mohamad E Allaf

*Author for correspondence: Tel.: +1 410 502 7710; Fax: +1 410 502 7711;

E-mail Address: mallaf@jhmi.edu

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

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Published Online:10 Apr 2019https://doi.org/10.2217/fon-2018-0951

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Abstract

Patients with high-risk renal cell carcinoma (RCC) experience high rates of recurrence despite definitive surgical resection. Recent trials of adjuvant tyrosine kinase inhibitor therapy have provided conflicting efficacy results at the cost of significant adverse events. PD-1 blockade via monoclonal antibodies has emerged as an effective disease-modifying treatment for metastatic RCC. There is emerging data across other solid tumors of the potential efficacy of neoadjuvant PD-1 blockade, and preclinical evidence supporting a neoadjuvant over adjuvant approach. PROSPER RCC is a Phase III, randomized trial evaluating whether perioperative nivolumab increases recurrence-free survival in patients with high-risk RCC undergoing nephrectomy. The neoadjuvant component, intended to prime the immune system for enhanced efficacy, distinguishes PROSPER from other purely adjuvant studies and permits highly clinically relevant translational studies.

While many patients with early stage kidney cancer can be cured by removal of the tumor and kidney (‘nephrectomy’), upward of 40% of patients can recur due to microscopic spread of the cancer prior to surgery. Adding anticancer drugs that are effective in the metastatic setting to surgery has potential to eliminate the microscopic disease and increase cure rates. The PROSPER renal cell carcinoma study is testing whether adding nivolumab, a drug that engages the immune system to better recognize, fight and eliminate the cancer, will improve disease control over surgery alone. Nivolumab will be given before and after surgery to see if it reduces the chance of the disease returning and decreases death from kidney cancer compared with patients receiving surgery only.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 15

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History

Received 23 December 2018

Accepted 6 March 2019

Published online 10 April 2019

Published in print May 2019

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Keywords

Supplementary data

An infographic accompanies this paper at the end of the references section. To download the infographic that accompanies this paper, please visit the journal website at: www.futuremedicine.com/doi/full/10.2217/fon-2018-0951

Acknowledgements

We would like to thank the patients and their families; J Manola (initial statistician); the ECOG-ACRIN Operations Team: G Ipock, J Corkery, A Bricker, S Archambault; and the many PROSPER co-investigators enrolling patients every day.

Financial & competing interests disclosure

The study is coordinated by the ECOG-ACRIN Cancer Research Group and supported by the National Cancer Institute. The study drug is provided by the Bristol-Myers Squibb under a Cooperative Research and Development Agreement with the National Cancer Institute. A Kapoor had research funding from Pfizer Oncology, Novartis Oncology, BMS and Roche. CG Drake is an advisor/consultant for BMS, Compugen, Roche/Genentech, Regeneron, AZ Medimmune and Merck; and a co-inventor on patents licensed from Johns Hopkins to AZ/Medimmune and to BMS. DYC Heng is an advisor for BMS, Pfizer, Novartis and Exelixis. PN Lara is a consultant for BMS. TK Choueiri has research funding from AstraZeneca, Bayer, BMS, Cerulean, Eisai, Foundation Medicine, Inc., Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products Limited, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group and Takeda; is a consultant/advisor to AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine, Inc., Exelixis, Genentech, Heron Therapeutics, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN and Analysis Group; and has received honoraria from AstraZeneca, Alexion, Sanofi/Aventis, Bayer, BMS, Cerulean, Eisai, Foundation Medicine, Inc., Exelixis, Genentech, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, NCCN, Michael J. Hennessy (MJH) Associates, Inc. (Healthcare Communications Company with several brands such as OnClive and PER), L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Medical Oncology, NEJM, Lancet Oncology and Heron Therapeutics. EA Singer has received research support from Astellas/Medivation, grant from the National Cancer Institute (P30CA072720). WM Stadler is a consultant for Astra-Zeneca, Bayer, BMS, Caremark/CVS, Clovis, Eisai, Genentech, Pfizer, research support (to institution): AbbVie, Astra-Zeneca, Bayer, Bristol-Myers-Squibb, Boehringer-Ingelheim, Calithera, Eisai, Exelixis, Genentech (Roche), Merck, Novartis, Pfizer, Tesaro, X4Pharmaceuticals; and has held miscellaneous/editorial roles for Cancer (ACS) and Up-To-Date. S Signoretti has received research support (to institution) from Exelixis, AstraZeneca, Bristol-Myers Squibb consultant: Merck, AstraZeneca/MedImmune, Verastem, American Association for Cancer Research and National Cancer Institute; and receives royalties for CDX2 antibody from BioGenex Laboratories. RT Gupta is a consultant for Bayer Pharma AG, Invivo Corp., and Bard; and is also on the speakers bureau for Bayer Pharma AG. MD Michaelson is an advisor for Pfizer, Novartis and Exelixis. DF McDermott is a consultant for Kidney Cancer Research: BMS, Pfizer, Merck, Novartis, Eisai, Exelixis, Array BioPharm and Genentech BioOncology; and has received research support from Kidney Cancer Research: Prometheus. D Cella is a consultant for Bristol-Myers Squibb, Bayer, Pfizer, Novartis, Aveo, Exelixis and Merck; and has received research support (to institution) from Bristol-Myers Squibb, Bayer, Pfizer, Novartis and GlaxoSmithKline. LI Wagner is a consultant for Celgene Inc. and Connect Myeloma registry. NB Haas is an advisor for Exelixis and Novartis. MA Carducci is an advisor for Astellas, Pfizer, Roche/Genentech, Merck, AbbVie; and has received research support (to institution) from Astra Zeneca, EMD Serrano, Pfizer, Bristol-Myers Squibb and Gilead. LC Harshman is an advisor for Bayer, Genentech, Dendreon, Pfizer, Medivation/Astellas, Kew Group, Theragene, Corvus, Merck, Exelixis; Novartis and Jounce; and has received research support (to institution) from Bayer, Sotio, Bristol-Myers Squib, Merck, Takeda, Dendreon/Valeant, Janssen, Medivation/Astellas, Genentech and Pfizer. ME Allaf has received research support from Progenics and is NIH funded (grant number: U10CA180820). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Trial registration

This study was registered on ClinicalTrials.gov (NCT03055013) as well as SWOG (CTSU/EA8143).

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