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

被引：22

作者：

Barroso-Sousa, Romualdo ^{[1
,2
,3
]}

Keenan, Tanya E. ^{[1
,2
]}

Li, Tianyu ^{[4
]}

Tayob, Nabihah ^{[5
]}

Trippa, Lorenzo ^{[4
]}

Pastorello, Ricardo G. ^{[6
]}

Richardson, Edward T., III ^{[6
]}

Dillon, Deborah ^{[6
]}

Amoozgar, Zohreh ^{[7
]}

Overmoyer, Beth ^{[1
,2
]}

Schnitt, Stuart J. ^{[6
]}

Winer, Eric P. ^{[1
,2
]}

Mittendorf, Elizabeth A. ^{[2
,8
]}

Van Allen, Eliezer ^{[1
,5
]}

Duda, Dan G. ^{[7
]}

Tolaney, Sara M. ^{[1
,2
]}

机构：

[1] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA

[2] Dana Farber Brigham & Womens Canc Ctr, Breast Oncol Program, Boston, MA USA

[3] Hosp Sirio Libanes, Oncol Ctr, Brasilia, DF, Brazil

[4] Dana Farber Canc Inst, Biostat, Boston, MA 02115 USA

[5] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[6] Brigham & Womens Hosp, Pathol, 75 Francis St, Boston, MA 02115 USA

[7] Massachusetts Gen Hosp, Steele Labs Tumor Biol, Boston, MA 02114 USA

[8] Brigham & Womens Hosp, Dept Surg, Div Breast Surg, 75 Francis St, Boston, MA 02115 USA

来源：

NPJ BREAST CANCER | 2021年 / 7卷 / 01期

基金：

美国国家卫生研究院;

关键词：

CLINICAL-OUTCOMES; BEVACIZUMAB; RESISTANCE; EXPRESSION; VEGF; IMMUNOTHERAPY; BLOCKADE; PATTERNS; FEATURES; THERAPY;

D O I：

10.1038/s41523-021-00287-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：8

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