Neoadjuvant pazopanib and molecular analysis of tissue response in renal cell carcinoma.

JCI Insight
Christopher G WoodW Kimryn Rathmell

Abstract

BACKGROUNDSurgery remains the frontline therapy for patients with localized clear cell renal cell carcinoma (ccRCC); however, 20%-40% recur. Angiogenesis inhibitors have improved survival in metastatic patients and may result in responses in the neoadjuvant setting. The impact of these agents on the tumor genetic heterogeneity or the immune milieu is largely unknown. This phase II study was designed to evaluate safety, response, and effect on tumor tissue of neoadjuvant pazopanib.METHODSccRCC patients with localized disease received pazopanib (800 mg daily; median 8 weeks), followed by nephrectomy. Five tumors were examined for mutations by whole exome sequencing from samples collected before therapy and at nephrectomy. These samples underwent RNA sequencing; 17 samples were available for posttreatment assessment.RESULTSTwenty-one patients were enrolled. The overall response rate was 8 of 21 (38%). No patients with progressive disease. At 1-year, response-free survival and overall survival was 83% and 89%, respectively. The most frequent grade 3 toxicity was hypertension (33%, 7 of 21). Sequencing revealed strong concordance between pre- and posttreatment samples within individual tumors, suggesting tumors harbor stable core pr...Continue Reading

References

Dec 19, 2003·The Urologic Clinics of North America·Nicolette K JanzenArie S Belldegrun
Jun 8, 2006·JAMA : the Journal of the American Medical Association·Robert J MotzerM Dror Michaelson
Jul 3, 2008·Cancer Research·Marcus SchmidtMathias Gehrmann
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Feb 4, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrew H BeckRobert B West
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Keith Syson ChanIrving L Weissman
Jan 27, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cora N SternbergRobert E Hawkins
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov
Oct 8, 2011·Breast Cancer Research : BCR·Achim RodyManfred Kaufmann
Mar 9, 2012·The New England Journal of Medicine·Marco GerlingerCharles Swanton
May 15, 2012·Bioinformatics·Christopher T SaundersR Keira Cheetham
May 29, 2012·Molecular Cancer Research : MCR·Eric JonaschW Kimryn Rathmell
Jun 12, 2012·Nature Genetics·Samuel Peña-LlopisJames Brugarolas
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jan 18, 2013·BMC Bioinformatics·Sonja HänzelmannJustin Guinney
Jun 25, 2013·Nature·UNKNOWN Cancer Genome Atlas Research Network
Jun 8, 2014·Bioinformatics·Lisle E MoseJoel S Parker
Jun 12, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael D IglesiaJonathan S Serody
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Oct 11, 2016·The New England Journal of Medicine·Alain RavaudUNKNOWN S-TRAC Investigators
Mar 7, 2017·Nature Methods·Rob PatroCarl Kingsford
Aug 15, 2017·Urologic Oncology·Ahmet BindayiIthaar H Derweesh
Jan 10, 2018·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Mar 22, 2018·The New England Journal of Medicine·Robert J MotzerUNKNOWN CheckMate 214 Investigators
Aug 24, 2018·The Journal of Clinical Investigation·Christof C SmithBenjamin G Vincent

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Methods Mentioned

BETA
biopsies
biopsy
xenografts
exome sequencing
Exome Capture

Clinical Trials Mentioned

NCT01361113

Software Mentioned

SnpEff
ABRA
Strelka
Salmon
STAR
R Foundation for Statistical Computing
SAS
TapeStation
FASTQC
NanoDrop

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