Neoadjuvant Nivolumab in Patients with High-risk Nonmetastatic Renal Cell Carcinoma.

May 31, 2021

Contributor: Michael A Gorin,Hiten D Patel,Steven P Rowe,Noah M Hahn,Hans J Hammers,Alice Pons,Bruce J Trock,Phillip M Pierorazio,Thomas R Nirschl,Daniela C Salles,Julie E Stein,Tamara L Lotan,Janis M Taube,Charles G Drake,Mohamad E Allaf

Neoadjuvant Nivolumab in Patients with High-risk Nonmetastatic Renal Cell Carcinoma.

Neoadjuvant immune checkpoint blockade represents a novel approach for potentially decreasing the risk of recurrence in patients with nonmetastatic renal cell carcinoma (RCC). In this early phase clincal tiral, we evaluated the safety and tolerability of neoadjuvant treatment with the programmed cell death protein 1 (PD-1) inhibitor nivolumab in patients with nonmetastatic high-risk RCC. Nonprimary endpoints included objective radiographic tumor response rate, immune-related pathologic response rate, quality of life alterations, and metastasis-free and overall survival. In total, 17 patients were enrolled in this study and underwent surgery without a delay after receiving three every-2-wk doses of neoadjuvant nivolumab. Adverse events (AEs) of any grade occurred in 14 (82.4%) patients, with two (11.8%) experiencing grade 3 events. Ten (58.8%) patients experienced an AE of any grade potentially attributable to nivolumab (all grade 1-2), and no grade 4-5 AEs occurred regardless of treatment attribution. The most common AEs were grade 1 fatigue (41.2%), grade 1 pruritis (29.4%), and grade 1 rash (29.4%). All evaluable patients had stable disease as per established radiographic criteria, with one (6.7%) demonstrating features of an immune-related pathologic response. Quality of life remained stable during treatment, with improvements relative to baseline noted at ≥6 mo postoperatively. Metastasis-free survival and overall survival were 85.1% and 100% at 2 yr, respectively. PATIENT SUMMARY: In this study, we evaluated the safety and tolerability of preoperative administration of three doses of the immune checkpoint inhibitor nivolumab in patients with clinically localized high-risk renal cell carcinoma. We demonstrated the safety of this approach and found that, although most patients will not experience a radiographic response to treatment, a subset may have features of an immune-related pathologic response.
Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Author

admin

View all posts

About The Expert

Michael A Gorin

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Hiten D Patel

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

Steven P Rowe

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Noah M Hahn

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Hans J Hammers

Division of Hematology-Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Alice Pons

Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg~Kimmel Institute for Cancer Immunotherapy and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Bruce J Trock

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

Phillip M Pierorazio

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Thomas R Nirschl

Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg~Kimmel Institute for Cancer Immunotherapy and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Daniela C Salles

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Julie E Stein

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Tamara L Lotan

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Janis M Taube

Bloomberg~Kimmel Institute for Cancer Immunotherapy and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Charles G Drake

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

Mohamad E Allaf

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: mallaf@jhmi.edu.

References

PubMed