Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study

Abstract This single-arm phase II study investigated the efficacy and safety of cabozantinib combined with nivolumab in metastatic triple-negative breast cancer (mTNBC). The primary endpoint was objective response rate (ORR) by RECIST 1.1. Biopsies at baseline and after cycle 1 were analyzed for tum...

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Autores principales:	Romualdo Barroso-Sousa, Tanya E. Keenan, Tianyu Li, Nabihah Tayob, Lorenzo Trippa, Ricardo G. Pastorello, Edward T. Richardson III, Deborah Dillon, Zohreh Amoozgar, Beth Overmoyer, Stuart J. Schnitt, Eric P. Winer, Elizabeth A. Mittendorf, Eliezer Van Allen, Dan G. Duda, Sara M. Tolaney
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1588be2699b0434ab5c7f6e1a6080ecb
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spelling	oai:doaj.org-article:1588be2699b0434ab5c7f6e1a6080ecb2021-12-02T15:09:17ZNivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study10.1038/s41523-021-00287-92374-4677https://doaj.org/article/1588be2699b0434ab5c7f6e1a6080ecb2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00287-9https://doaj.org/toc/2374-4677Abstract This single-arm phase II study investigated the efficacy and safety of cabozantinib combined with nivolumab in metastatic triple-negative breast cancer (mTNBC). The primary endpoint was objective response rate (ORR) by RECIST 1.1. Biopsies at baseline and after cycle 1 were analyzed for tumor-infiltrating lymphocytes (TILs), PD-L1, and whole-exome and transcriptome sequencing. Only 1/18 patients achieved a partial response (ORR 6%), and the trial was stopped early. Toxicity led to cabozantinib dose reduction in 50% of patients. One patient had a PD-L1-positive tumor, and three patients had TILs > 10%. The responding patient had a PD-L1-negative tumor with low tumor mutational burden but high TILs and enriched immune gene expression. High pretreatment levels of plasma immunosuppressive cytokines, chemokines, and immune checkpoint molecules were associated with rapid progression. Although this study did not meet its primary endpoint, immunostaining, genomic, and proteomic studies indicated a high degree of tumor immunosuppression in this mTNBC cohort.Romualdo Barroso-SousaTanya E. KeenanTianyu LiNabihah TayobLorenzo TrippaRicardo G. PastorelloEdward T. Richardson IIIDeborah DillonZohreh AmoozgarBeth OvermoyerStuart J. SchnittEric P. WinerElizabeth A. MittendorfEliezer Van AllenDan G. DudaSara M. TolaneyNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Romualdo Barroso-Sousa Tanya E. Keenan Tianyu Li Nabihah Tayob Lorenzo Trippa Ricardo G. Pastorello Edward T. Richardson III Deborah Dillon Zohreh Amoozgar Beth Overmoyer Stuart J. Schnitt Eric P. Winer Elizabeth A. Mittendorf Eliezer Van Allen Dan G. Duda Sara M. Tolaney Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
description	Abstract This single-arm phase II study investigated the efficacy and safety of cabozantinib combined with nivolumab in metastatic triple-negative breast cancer (mTNBC). The primary endpoint was objective response rate (ORR) by RECIST 1.1. Biopsies at baseline and after cycle 1 were analyzed for tumor-infiltrating lymphocytes (TILs), PD-L1, and whole-exome and transcriptome sequencing. Only 1/18 patients achieved a partial response (ORR 6%), and the trial was stopped early. Toxicity led to cabozantinib dose reduction in 50% of patients. One patient had a PD-L1-positive tumor, and three patients had TILs > 10%. The responding patient had a PD-L1-negative tumor with low tumor mutational burden but high TILs and enriched immune gene expression. High pretreatment levels of plasma immunosuppressive cytokines, chemokines, and immune checkpoint molecules were associated with rapid progression. Although this study did not meet its primary endpoint, immunostaining, genomic, and proteomic studies indicated a high degree of tumor immunosuppression in this mTNBC cohort.
format	article
author	Romualdo Barroso-Sousa Tanya E. Keenan Tianyu Li Nabihah Tayob Lorenzo Trippa Ricardo G. Pastorello Edward T. Richardson III Deborah Dillon Zohreh Amoozgar Beth Overmoyer Stuart J. Schnitt Eric P. Winer Elizabeth A. Mittendorf Eliezer Van Allen Dan G. Duda Sara M. Tolaney
author_facet	Romualdo Barroso-Sousa Tanya E. Keenan Tianyu Li Nabihah Tayob Lorenzo Trippa Ricardo G. Pastorello Edward T. Richardson III Deborah Dillon Zohreh Amoozgar Beth Overmoyer Stuart J. Schnitt Eric P. Winer Elizabeth A. Mittendorf Eliezer Van Allen Dan G. Duda Sara M. Tolaney
author_sort	Romualdo Barroso-Sousa
title	Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
title_short	Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
title_full	Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
title_fullStr	Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
title_full_unstemmed	Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study
title_sort	nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase ii and biomarker study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1588be2699b0434ab5c7f6e1a6080ecb
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Nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer: a phase II and biomarker study

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