Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients

Autor: Sean T. Glenn, Antonios Papanicolau-Sengos, Jeffrey M. Conroy, Blake Burgher, Keisuke Shirai, Carl Morrison, Rajan T. Gupta, Jason Zhu, Konstantin H. Dragnev, Pooja Ghatalia, Razelle Kurzrock, Mary Nesline, Saby George, Vincent Giamo, Wiam Bshara, Tian Zhang, Felicia L. Lenzo, Katherine G. Madden, Matthew Labriola, Bo Xu, Michelle S Park, Matthew Zibelman, Jonathan Andreas, Rajbir Singh, Robert Edwards, Daniel J. George, Shannon J. McCall, Robin Jacob, Yirong Wang, Laura J. Tafe, Farshid Dayyani, Sarabjot Pabla
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Kidney Disease
Immune checkpoint inhibitors
medicine.medical_treatment
urologic and male genital diseases
0302 clinical medicine
Antineoplastic Agents
Immunological

Renal cell carcinoma
PD-1
Immunology and Allergy
Medicine
RC254-282
Original Research
Cancer
biology
ki-67
pd-1
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Middle Aged
Progression-Free Survival
Immunological
Nivolumab
Oncology
030220 oncology & carcinogenesis
Ki-67
Immunohistochemistry
Female
Immunotherapy
Research Article
Adult
PD-L1
renal cell carcinoma
proliferation
Immunology
Oncology and Carcinogenesis
Antineoplastic Agents
03 medical and health sciences
pd-l1
Genetics
Humans
Carcinoma
Renal Cell

Aged
nivolumab
business.industry
Carcinoma
Renal Cell
RC581-607
medicine.disease
Clear cell renal cell carcinoma
030104 developmental biology
Good Health and Well Being
Cancer research
biology.protein
Immunologic diseases. Allergy
business
Zdroj: Oncoimmunology, vol 9, iss 1
OncoImmunology, Vol 9, Iss 1 (2020)
Oncoimmunology
article-version (VoR) Version of Record
Popis: 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.
Databáze: OpenAIRE
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