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Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
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....
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458647/ https://www.ncbi.nlm.nih.gov/pubmed/32923131 http://dx.doi.org/10.1080/2162402X.2020.1773200 |
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author | Zhang, Tian Pabla, Sarabjot Lenzo, Felicia L. Conroy, Jeffrey M. Nesline, Mary K. Glenn, Sean T. Papanicolau-Sengos, Antonios Burgher, Blake Giamo, Vincent Andreas, Jonathan Wang, Yirong Bshara, Wiam Madden, Katherine G. Shirai, Keisuke Dragnev, Konstantin Tafe, Laura J. Gupta, Rajan Zhu, Jason Labriola, Matthew McCall, Shannon George, Daniel J. Ghatalia, Pooja Dayyani, Farshid Edwards, Robert Park, Michelle S Singh, Rajbir Jacob, Robin George, Saby Xu, Bo Zibelman, Matthew Kurzrock, Razelle Morrison, Carl |
author_facet | Zhang, Tian Pabla, Sarabjot Lenzo, Felicia L. Conroy, Jeffrey M. Nesline, Mary K. Glenn, Sean T. Papanicolau-Sengos, Antonios Burgher, Blake Giamo, Vincent Andreas, Jonathan Wang, Yirong Bshara, Wiam Madden, Katherine G. Shirai, Keisuke Dragnev, Konstantin Tafe, Laura J. Gupta, Rajan Zhu, Jason Labriola, Matthew McCall, Shannon George, Daniel J. Ghatalia, Pooja Dayyani, Farshid Edwards, Robert Park, Michelle S Singh, Rajbir Jacob, Robin George, Saby Xu, Bo Zibelman, Matthew Kurzrock, Razelle Morrison, Carl |
author_sort | Zhang, Tian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7458647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-74586472020-09-11 Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients Zhang, Tian Pabla, Sarabjot Lenzo, Felicia L. Conroy, Jeffrey M. Nesline, Mary K. Glenn, Sean T. Papanicolau-Sengos, Antonios Burgher, Blake Giamo, Vincent Andreas, Jonathan Wang, Yirong Bshara, Wiam Madden, Katherine G. Shirai, Keisuke Dragnev, Konstantin Tafe, Laura J. Gupta, Rajan Zhu, Jason Labriola, Matthew McCall, Shannon George, Daniel J. Ghatalia, Pooja Dayyani, Farshid Edwards, Robert Park, Michelle S Singh, Rajbir Jacob, Robin George, Saby Xu, Bo Zibelman, Matthew Kurzrock, Razelle Morrison, Carl Oncoimmunology Original Research 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. Taylor & Francis 2020-06-10 /pmc/articles/PMC7458647/ /pubmed/32923131 http://dx.doi.org/10.1080/2162402X.2020.1773200 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Zhang, Tian Pabla, Sarabjot Lenzo, Felicia L. Conroy, Jeffrey M. Nesline, Mary K. Glenn, Sean T. Papanicolau-Sengos, Antonios Burgher, Blake Giamo, Vincent Andreas, Jonathan Wang, Yirong Bshara, Wiam Madden, Katherine G. Shirai, Keisuke Dragnev, Konstantin Tafe, Laura J. Gupta, Rajan Zhu, Jason Labriola, Matthew McCall, Shannon George, Daniel J. Ghatalia, Pooja Dayyani, Farshid Edwards, Robert Park, Michelle S Singh, Rajbir Jacob, Robin George, Saby Xu, Bo Zibelman, Matthew Kurzrock, Razelle Morrison, Carl Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients |
title | Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients |
title_full | Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients |
title_fullStr | Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients |
title_full_unstemmed | Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients |
title_short | Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients |
title_sort | proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458647/ https://www.ncbi.nlm.nih.gov/pubmed/32923131 http://dx.doi.org/10.1080/2162402X.2020.1773200 |
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