@article{a1581992660c4816ab425688f50c0a7e,
title = "Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients",
abstract = "Background: Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice. Methods: Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome. Results: For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%). Conclusions: Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings.",
keywords = "Ki-67, Nivolumab, PD-1, PD-L1, proliferation, renal cell carcinoma",
author = "Tian Zhang and Sarabjot Pabla and Lenzo, {Felicia L.} and Conroy, {Jeffrey M.} and Nesline, {Mary K.} and Glenn, {Sean T.} and Antonios Papanicolau-Sengos and Blake Burgher and Vincent Giamo and Jonathan Andreas and Yirong Wang and Wiam Bshara and Madden, {Katherine G.} and Keisuke Shirai and Konstantin Dragnev and Tafe, {Laura J.} and Rajan Gupta and Jason Zhu and Matthew Labriola and Shannon McCall and George, {Daniel J.} and Pooja Ghatalia and Farshid Dayyani and Robert Edwards and Park, {Michelle S.} and Rajbir Singh and Robin Jacob and Saby George and Bo Xu and Matthew Zibelman and Razelle Kurzrock and Carl Morrison",
note = "Funding Information: MZ, PG, KD, KS, KGM, LJT, DM, JZ, ML, RS, SM, RE, MP, and RJ have no competing interests to disclose. SP, JMC, MKN, STG, APS, BB. JH, VG, JA, FLL, YW, and CM are employees of OmniSeq, Inc. (Buffalo, NY) and hold restricted stock in OmniSeq, Inc. SG, BX, WB, CM, STG, and JMC are employees of Roswell Park Comprehensive Cancer Center (Buffalo, NY), which is the majority shareholder of OmniSeq, Inc. TZ has received consulting fees from Genentech Roche, Sanofi-Aventis, Astra Zeneca, Bayer, Janssen, Pfizer, Foundation Medicine, Pharmacyclics, Bristol Myers Squibb, and Amgen, promotional service fees from Genentech Roche, Exelixis, and Sanofi Genzyme, contracted research with Janssen, Pfizer, OmniSeq, PGDx, Novartis, Merrimack, Abbvie/StemCentrx, Acerta, Merck, and Regeneron, and ownership interest in Capio Biosciences. FD has consulted for Roche Diagnostics Int, Exelixis, Eisai, and Genentech, and has participated in speakers bureaus for Genentech, Amgen, Bayer, Ipsen, and Sirtex. RK, has research funding from Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Guardant Health, Grifols, and Konica Minolta, as well as consultant fees from LOXO, X-Biotech, Actuate Therapeutics, Roche, and NeoMed, and receives speaker fees from Roche, and has equity in IDbyDNA, and CureMatch, Inc. Funding Information: This research was funded by OmniSeq, Inc. (Buffalo, NY). Publisher Copyright: {\textcopyright} 2020, {\textcopyright} 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2020",
month = jan,
day = "1",
doi = "10.1080/2162402X.2020.1773200",
language = "English (US)",
volume = "9",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",
number = "1",
}