EURURO Vol. 72 No. 4

557 656

Platinum Priority – Kidney Cancer
Editorial by John T. Leppert on pp. 565–566 of this issue
Evolution of Circulating Tumor DNA Profile from First-line to
Subsequent Therapy in Metastatic Renal Cell Carcinoma
Sumanta K. Pal Guru Sonpavde Neeraj Agarwal Nicholas J. Vogelzang Sandy Srinivas
Naomi B. Haas Sabina Signoretti Bradley A. McGregor Jeremy Jones Richard B. Lanman
Kimberly C. Banks Toni K. Choueiri
a Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; bDivision of Hematology &
Oncology, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL, USA; c Division of[3_TD$DIFF] Medical Oncology, [4_TD$DIFF]Department [5_TD$DIFF]of [6_TD$DIFF]Internal
[7_TD$DIFF]Medicine, University of Utah[8_TD$DIFF] Huntsman Cancer Institute, Salt Lake City, UT, USA; d Department of Medical Oncology, Nevada Comprehensive Cancer Center,
Las Vegas, NV, USA; e Department of Medicine, Stanford University, Stanford, CA, USA; f Division of Hematology/Medical Oncology, Abramson Cancer Center
of the University of Pennsylvania, Philadelphia, PA, USA; g Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA,
USA; hDepartment of Medical Oncology, Dana-Farber Cancer Institute/Brigham and Women’s Cancer Center, Boston, MA, USA; i Department of Cancer
Biology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA; j Department of Medical Affairs, Guardant Health, Inc., Redwood City, CA, USA
ava ilable at
journal homepage:
Article info
Article history:
Accepted March 29, 2017
Associate Editor:
James Catto
Keywords:
Biomarkers
Cell-free DNA
Circulating tumor DNA
Next generation sequencing
Renal cell carcinoma
Abstract
Background: Treatment of metastatic renal cell carcinoma (mRCC) typically entails
mechanistically distinct agents across the first- and second-line setting. Activity of these
agents may be predicated on selective pressure that modulates RCC biology. Circulating
tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in
genomic profile.
Objective: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess
changes across patients receiving first-line and later lines of therapy.
Design, setting, and participants: We obtained the ctDNA profile in mRCC patients who
received ctDNA profiling as part of routine clinical care at progression using a 73-gene
Clinical Laboratory Improvement Amendments-certified ctDNA platform.
Outcome measurements and statistical analysis: Genomic alterations (GAs) were
pooled for the entire cohort. A comparison of first- and postfirst-line was performed
with grouping based on conventional practice patterns (first-line regimens included
sunitinib, pazopanib, and bevacizumab, and postfirst-line regimens included everoli-
mus, axitinib, cabozantinib, and nivolumab).
Results and limitations: ctDNA clinical results from a nationwide cohort of 220 conse-
cutive patients with mRCC were assessed (145 men, 75 women; median age: 63 yr,
interquartile range: 57–70). GAs were detected in 78.6% of patients. The most frequent
GAs in the overall cohort included TP53 (35%), VHL (23%), EGFR (17%), NF1 (16%), and
ARID1A (12%). Thirty-eight and 64 patients were coded as receiving first-line and later
line agents, respectively. The highest disparity in GA frequencies in postfirst-line versus
first-line were in TP53 (49% vs 24%), VHL (29% vs 18%), NF1 (20% vs 3%), EGFR (15% vs 8%),
and PIK3CA (17% vs 8%) while ARID1A was equivalent (13% vs 11%). Restricting the
analysis to later lines versus first-line vascular endothelial growth factor inhibitors,
these differences were even more prominent, particularly for TP53 (64% vs 31%) and NF1
(29% vs 4%).
* Corresponding author. City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte,
CA 91010, USA. Tel. +1 626 256 4673; Fax: +1 626 301 8233.
E-mail address: (S.K. Pal).
0302-2838/# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.