TY - JOUR
T1 - Biomarkers of immunotherapy in urothelial and renal cell carcinoma
T2 - PD-L1, tumor mutational burden, and beyond
AU - Zhu, Jason
AU - Armstrong, Andrew J.
AU - Friedlander, Terence W.
AU - Kim, Won
AU - Pal, Sumanta K.
AU - George, Daniel J.
AU - Zhang, Tian
N1 - Funding Information:
JZ has no financial or non-financial competing interests. AJA reports research funding from Dendreon, Sanofi, Bayer, Pfizer, Novartis, Janssen, Medivation, Astellas Pharma, Gilead Sciences, Genentech, and Active Biotech; consultant/ advisory roles from Bayer, Sanofi, Novartis, Dendreon, Medivation, Janssen, and Pfizer; and speakers’ bureau for Dendreon and Sanofi. TWF reports research funding from Janssen, ImClone Systems, Aragon Pharmaceuticals, and GlaxoSmithKline; consultant/advisory role for Pfizer, Genentech, AstraZeneca, and Clovis Oncology; and speakers’ bureau for Sanofi, Dendreon, and Astel-las/Medivation. WK reports consultant/advisory roles for Dendreon, Bayer, and Genentech. SKP reports research funding from Medivation; consulting/ advisory roles for Pfizer, Novartis, Aveo, Myriad Pharmaceuticals, Genentech, Exelixis, Bristol-Myers Squibb, Astellas Pharma, Ipsen, and Eisai. DJG reports research funding from Exelixis, Genentech, Janssen, Novartis, Pfizer, Viamet Pharmaceuticals, Astellas Pharma, Bristol-Myers Squibb, Millennium, Acerta Pharma, Bayer, GlaxoSmithKline, Dendreon, AstraZeneca, and Sanofi; consultant/advisory roles from Bayer, Dendreon, Exelixis, Medivation, Novartis, Pfizer, Sanofi, GSK, Astellas Pharma, Innocrin Pharma, Bristol Myers Squibb, Genentech, Janssen, Acceleron Pharma, Celgene, Merck Sharp & Dohme, and Myovant Sciences; and speakers’ bureau for Dendreon, Novartis, Sanofi, and Bayer. TZ reports research funding from Janssen, Pfizer, Acerta Pharma, Novartis, Regeneron, and Stemcentrx; consultant/advisory roles for Janssen, Bayer, Genentech, Sanofi, and Exelixis; and ownership/employment (spouse) in Capio BioSciences.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/1/25
Y1 - 2018/1/25
N2 - Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility. Further limitations include the use of archival specimens to measure this dynamic biomarker. Indeed, until PD-L1 testing is standardized and can consistently predict treatment outcome, the currently available PD-L1 assays are not clinically useful in urothelial and renal cell carcinoma. Other more promising biomarkers include tumor mutational burden, profiles of tumor infiltrating lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker may be best but will need prospective testing to validate such a biomarker.
AB - Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility. Further limitations include the use of archival specimens to measure this dynamic biomarker. Indeed, until PD-L1 testing is standardized and can consistently predict treatment outcome, the currently available PD-L1 assays are not clinically useful in urothelial and renal cell carcinoma. Other more promising biomarkers include tumor mutational burden, profiles of tumor infiltrating lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker may be best but will need prospective testing to validate such a biomarker.
KW - Biomarkers
KW - Immune checkpoint inhibition
KW - PD-L1
KW - Renal cell carcinoma
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85041001162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041001162&partnerID=8YFLogxK
U2 - 10.1186/s40425-018-0314-1
DO - 10.1186/s40425-018-0314-1
M3 - Review article
C2 - 29368638
AN - SCOPUS:85041001162
SN - 2051-1426
VL - 6
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 1
M1 - 4
ER -