Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients.
Ki-67
Nivolumab
PD-1
PD-L1
proliferation
renal cell carcinoma
Journal
Oncoimmunology
ISSN: 2162-4011
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
10 06 2020
10 06 2020
Historique:
entrez:
14
9
2020
pubmed:
15
9
2020
medline:
15
9
2020
Statut:
epublish
Résumé
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. Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome. 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 ( 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.
Sections du résumé
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 (
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.
Identifiants
pubmed: 32923131
doi: 10.1080/2162402X.2020.1773200
pii: 1773200
pmc: PMC7458647
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Nivolumab
31YO63LBSN
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
1773200Informations de copyright
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
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