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Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A)
To determine the value of tumor cell programmed death-ligand 1 (PD-L1) expression as a predictive biomarker of nivolumab monotherapy efficacy in treatment-naive patients with clear cell renal cell carcinoma (ccRCC) and the efficacy of salvage nivolumab/ipilimumab in patients with tumors unresponsive...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer Health
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426835/ https://www.ncbi.nlm.nih.gov/pubmed/35442713 http://dx.doi.org/10.1200/JCO.21.02938 |
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author | Atkins, Michael B. Jegede, Opeyemi A. Haas, Naomi B. McDermott, David F. Bilen, Mehmet A. Stein, Mark Sosman, Jeffrey A. Alter, Robert Plimack, Elizabeth R. Ornstein, Moshe Hurwitz, Michael Peace, David J. Signoretti, Sabina Denize, Thomas Cimadamore, Alessia Wu, Catherine J. Braun, David Einstein, David Catalano, Paul J. Hammers, Hans |
author_facet | Atkins, Michael B. Jegede, Opeyemi A. Haas, Naomi B. McDermott, David F. Bilen, Mehmet A. Stein, Mark Sosman, Jeffrey A. Alter, Robert Plimack, Elizabeth R. Ornstein, Moshe Hurwitz, Michael Peace, David J. Signoretti, Sabina Denize, Thomas Cimadamore, Alessia Wu, Catherine J. Braun, David Einstein, David Catalano, Paul J. Hammers, Hans |
author_sort | Atkins, Michael B. |
collection | PubMed |
description | To determine the value of tumor cell programmed death-ligand 1 (PD-L1) expression as a predictive biomarker of nivolumab monotherapy efficacy in treatment-naive patients with clear cell renal cell carcinoma (ccRCC) and the efficacy of salvage nivolumab/ipilimumab in patients with tumors unresponsive to nivolumab monotherapy. METHODS: Eligible patients with treatment-naive ccRCC received nivolumab until progressive disease (PD), toxicity, or completing 96 treatment weeks (part A). Patients with PD before or stable disease at 48 weeks could receive salvage nivolumab/ipilimumab (part B). The primary end point was improvement in 1-year progression-free survival in patients with tumor PD-L1 expression > 20% versus 0%. RESULTS: One hundred twenty-three patients were enrolled. The objective response rate (ORR) was 34.1% (95% CI, 25.8 to 43.2). ORR by International Metastatic RCC Database Consortium category was favorable-risk 57.1%, intermediate-risk/poor-risk 25.0%, and by sarcomatoid features 36.4%. The ORR was 26.9%, 50.0%, and 75.0% for patients with the tumor PD-L1 expression of 0, 1-20, or > 20%, respectively (trend test P value = .002). The median duration of response was 27.6 (19.3 to not reached) months, with 26 of 42 responders including 17 of 20 with favorable-risk disease remaining progression-free. The 1-year progression-free survival was 34.6% and 75.0% in the PD-L1 = 0% and > 20% categories, respectively (P = .050). Ninety-seven patients with PD or prolonged stable disease were potentially eligible for part B, and 35 were enrolled. The ORR for part B was 11.4%. Grade ≥ 3 treatment-related adverse events occurred in 35% of patients on nivolumab and 43% of those on salvage nivolumab/ipilimumab. CONCLUSION: Nivolumab monotherapy is active in treatment-naive ccRCC. Although efficacy appears to be less than that of nivolumab/ipilimumab in patients with intermediate-risk/poor-risk disease, favorable-risk patients had notable benefit. Efficacy correlated with tumor PD-L1 status. Salvage nivolumab/ipilimumab was frequently not feasible and of limited benefit. |
format | Online Article Text |
id | pubmed-9426835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Wolters Kluwer Health |
record_format | MEDLINE/PubMed |
spelling | pubmed-94268352023-09-01 Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A) Atkins, Michael B. Jegede, Opeyemi A. Haas, Naomi B. McDermott, David F. Bilen, Mehmet A. Stein, Mark Sosman, Jeffrey A. Alter, Robert Plimack, Elizabeth R. Ornstein, Moshe Hurwitz, Michael Peace, David J. Signoretti, Sabina Denize, Thomas Cimadamore, Alessia Wu, Catherine J. Braun, David Einstein, David Catalano, Paul J. Hammers, Hans J Clin Oncol ORIGINAL REPORTS To determine the value of tumor cell programmed death-ligand 1 (PD-L1) expression as a predictive biomarker of nivolumab monotherapy efficacy in treatment-naive patients with clear cell renal cell carcinoma (ccRCC) and the efficacy of salvage nivolumab/ipilimumab in patients with tumors unresponsive to nivolumab monotherapy. METHODS: Eligible patients with treatment-naive ccRCC received nivolumab until progressive disease (PD), toxicity, or completing 96 treatment weeks (part A). Patients with PD before or stable disease at 48 weeks could receive salvage nivolumab/ipilimumab (part B). The primary end point was improvement in 1-year progression-free survival in patients with tumor PD-L1 expression > 20% versus 0%. RESULTS: One hundred twenty-three patients were enrolled. The objective response rate (ORR) was 34.1% (95% CI, 25.8 to 43.2). ORR by International Metastatic RCC Database Consortium category was favorable-risk 57.1%, intermediate-risk/poor-risk 25.0%, and by sarcomatoid features 36.4%. The ORR was 26.9%, 50.0%, and 75.0% for patients with the tumor PD-L1 expression of 0, 1-20, or > 20%, respectively (trend test P value = .002). The median duration of response was 27.6 (19.3 to not reached) months, with 26 of 42 responders including 17 of 20 with favorable-risk disease remaining progression-free. The 1-year progression-free survival was 34.6% and 75.0% in the PD-L1 = 0% and > 20% categories, respectively (P = .050). Ninety-seven patients with PD or prolonged stable disease were potentially eligible for part B, and 35 were enrolled. The ORR for part B was 11.4%. Grade ≥ 3 treatment-related adverse events occurred in 35% of patients on nivolumab and 43% of those on salvage nivolumab/ipilimumab. CONCLUSION: Nivolumab monotherapy is active in treatment-naive ccRCC. Although efficacy appears to be less than that of nivolumab/ipilimumab in patients with intermediate-risk/poor-risk disease, favorable-risk patients had notable benefit. Efficacy correlated with tumor PD-L1 status. Salvage nivolumab/ipilimumab was frequently not feasible and of limited benefit. Wolters Kluwer Health 2022-09-01 2022-04-20 /pmc/articles/PMC9426835/ /pubmed/35442713 http://dx.doi.org/10.1200/JCO.21.02938 Text en © 2022 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | ORIGINAL REPORTS Atkins, Michael B. Jegede, Opeyemi A. Haas, Naomi B. McDermott, David F. Bilen, Mehmet A. Stein, Mark Sosman, Jeffrey A. Alter, Robert Plimack, Elizabeth R. Ornstein, Moshe Hurwitz, Michael Peace, David J. Signoretti, Sabina Denize, Thomas Cimadamore, Alessia Wu, Catherine J. Braun, David Einstein, David Catalano, Paul J. Hammers, Hans Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A) |
title | Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A) |
title_full | Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A) |
title_fullStr | Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A) |
title_full_unstemmed | Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A) |
title_short | Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A) |
title_sort | phase ii study of nivolumab and salvage nivolumab/ipilimumab in treatment-naive patients with advanced clear cell renal cell carcinoma (hcrn gu16-260-cohort a) |
topic | ORIGINAL REPORTS |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426835/ https://www.ncbi.nlm.nih.gov/pubmed/35442713 http://dx.doi.org/10.1200/JCO.21.02938 |
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