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Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab

The combination of ipilimumab plus nivolumab (I+N) has greatly improved outcomes in patients with intermediate or poor-risk untreated metastatic renal cell carcinoma (mRCC). However, little is known about the outcomes of patients with brain metastasis (BrM) treated with I+N. A search was performed t...

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Autores principales: Brown, Landon C., Desai, Kunal, Wei, Wei, Kinsey, Emily N., Kao, Chester, George, Daniel J., Rini, Brian I., Ornstein, Moshe C., Zhang, Tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438842/
https://www.ncbi.nlm.nih.gov/pubmed/34518292
http://dx.doi.org/10.1136/jitc-2021-003281
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author Brown, Landon C.
Desai, Kunal
Wei, Wei
Kinsey, Emily N.
Kao, Chester
George, Daniel J.
Rini, Brian I.
Ornstein, Moshe C.
Zhang, Tian
author_facet Brown, Landon C.
Desai, Kunal
Wei, Wei
Kinsey, Emily N.
Kao, Chester
George, Daniel J.
Rini, Brian I.
Ornstein, Moshe C.
Zhang, Tian
author_sort Brown, Landon C.
collection PubMed
description The combination of ipilimumab plus nivolumab (I+N) has greatly improved outcomes in patients with intermediate or poor-risk untreated metastatic renal cell carcinoma (mRCC). However, little is known about the outcomes of patients with brain metastasis (BrM) treated with I+N. A search was performed to retrospectively identify all patients with mRCC treated with I+N in the Duke Cancer Institute and the Cleveland Clinic Taussig Cancer Center, followed by a chart review. Patients were included if they had BrM at the time of I+N initiation. Cohort characteristics are summarized with descriptive statistics. Kaplan-Meier method was used to estimate overall survival (OS) and global, intracranial, and extracranial progression-free survival (PFS) for the cohort and log rank test was used to compare OS and PFS between patient groups. Radiographic response was categorized by RECIST. Fisher’s exact test was used to correlate patient factors with radiographic response. From October 2017 to December 2020, 19 patients with BrM received I+N for mRCC with a median follow-up time of 27.1 months (range 15.0–35.6). By International Metastatic RCC Database Consortium (IMDC) risk criteria, 16% had favorable, 58% had intermediate, and 26% had poor-risk disease. 68% were systemic therapy naïve, and 77% of patients had clear cell histology. 95% had received local CNS directed therapy with surgery, radiotherapy, or both. The objective response rate was 44% (0% complete response) with three of six patients treated in the second line or greater setting experiencing a partial response. The median PFS was 7.6 months (95% CI 5.6 to 14.9). The median extracranial PFS was 8.5 months (95% CI 5.6 to 19.7), and median intracranial PFS was 14.7 months (95% CI 7.2 to not reached). No variables assessed were significantly associated with radiographic response (gender, IMDC risk, presence of bone metastasis, line of therapy, or presence of immune related adverse events). In our retrospective cohort of patients with mRCC with BrM, I+N, in combination with CNS-directed local therapy, appears to have clinical efficacy as previously described with responses seen beyond the first-line setting. Further investigation is warranted in this population given exclusion from prior clinical trials.
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spelling pubmed-84388422021-09-24 Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab Brown, Landon C. Desai, Kunal Wei, Wei Kinsey, Emily N. Kao, Chester George, Daniel J. Rini, Brian I. Ornstein, Moshe C. Zhang, Tian J Immunother Cancer Clinical/Translational Cancer Immunotherapy The combination of ipilimumab plus nivolumab (I+N) has greatly improved outcomes in patients with intermediate or poor-risk untreated metastatic renal cell carcinoma (mRCC). However, little is known about the outcomes of patients with brain metastasis (BrM) treated with I+N. A search was performed to retrospectively identify all patients with mRCC treated with I+N in the Duke Cancer Institute and the Cleveland Clinic Taussig Cancer Center, followed by a chart review. Patients were included if they had BrM at the time of I+N initiation. Cohort characteristics are summarized with descriptive statistics. Kaplan-Meier method was used to estimate overall survival (OS) and global, intracranial, and extracranial progression-free survival (PFS) for the cohort and log rank test was used to compare OS and PFS between patient groups. Radiographic response was categorized by RECIST. Fisher’s exact test was used to correlate patient factors with radiographic response. From October 2017 to December 2020, 19 patients with BrM received I+N for mRCC with a median follow-up time of 27.1 months (range 15.0–35.6). By International Metastatic RCC Database Consortium (IMDC) risk criteria, 16% had favorable, 58% had intermediate, and 26% had poor-risk disease. 68% were systemic therapy naïve, and 77% of patients had clear cell histology. 95% had received local CNS directed therapy with surgery, radiotherapy, or both. The objective response rate was 44% (0% complete response) with three of six patients treated in the second line or greater setting experiencing a partial response. The median PFS was 7.6 months (95% CI 5.6 to 14.9). The median extracranial PFS was 8.5 months (95% CI 5.6 to 19.7), and median intracranial PFS was 14.7 months (95% CI 7.2 to not reached). No variables assessed were significantly associated with radiographic response (gender, IMDC risk, presence of bone metastasis, line of therapy, or presence of immune related adverse events). In our retrospective cohort of patients with mRCC with BrM, I+N, in combination with CNS-directed local therapy, appears to have clinical efficacy as previously described with responses seen beyond the first-line setting. Further investigation is warranted in this population given exclusion from prior clinical trials. BMJ Publishing Group 2021-09-13 /pmc/articles/PMC8438842/ /pubmed/34518292 http://dx.doi.org/10.1136/jitc-2021-003281 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Clinical/Translational Cancer Immunotherapy
Brown, Landon C.
Desai, Kunal
Wei, Wei
Kinsey, Emily N.
Kao, Chester
George, Daniel J.
Rini, Brian I.
Ornstein, Moshe C.
Zhang, Tian
Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab
title Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab
title_full Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab
title_fullStr Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab
title_full_unstemmed Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab
title_short Clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab
title_sort clinical outcomes in patients with metastatic renal cell carcinoma and brain metastasis treated with ipilimumab and nivolumab
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438842/
https://www.ncbi.nlm.nih.gov/pubmed/34518292
http://dx.doi.org/10.1136/jitc-2021-003281
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