Clinical Activity and Safety of Cabozantinib for Brain Metastases in Patients With Renal Cell Carcinoma

被引:52
作者
Hirsch, Laure [1 ,2 ]
Chanza, Nieves Martinez [1 ,3 ]
Farah, Subrina [4 ]
Xie, Wanling [4 ]
Flippot, Ronan [2 ]
Braun, David A. [1 ]
Rathi, Nityam [5 ]
Thouvenin, Jonathan [6 ]
Collier, Katharine A. [7 ]
Seront, Emmanuel [8 ]
de Velasco, Guillermo [9 ]
Dzimitrowicz, Hannah [10 ]
Beuselinck, Benoit [11 ]
Xu, Wenxin [1 ,12 ]
Bowman, I. Alex [13 ]
Lam, Elaine T. [14 ]
Abuqayas, Bashar [15 ]
Bilen, Mehmet Asim [16 ]
Varkaris, Andreas [12 ]
Zakharia, Yousef [15 ]
Harrison, Michael R. [10 ]
Mortazavi, Amir [7 ]
Barthelemy, Philippe [6 ]
Agarwal, Neeraj [5 ]
McKay, Rana R. [17 ]
Brastianos, Priscilla K. [18 ]
Krajewski, Katherine M. [19 ]
Albiges, Laurence [2 ]
Harshman, Lauren C. [1 ]
Choueiri, Toni K. [1 ]
机构
[1] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave, Boston, MA 02115 USA
[2] Gustave Roussy, Dept Med Oncol, Villejuif, France
[3] Univ Libre Bruxelles, Jules Bordet Inst, Med Oncol Dept, Brussels, Belgium
[4] Dana Farber Canc Inst, Dept Data Sci, Boston, MA 02115 USA
[5] Huntsman Canc Inst, Salt Lake City, UT USA
[6] Univ Strasbourg, Inst Cancerol Strasbourg Europe, Dept Med Oncol, Hop Univ Strasbourg, Strasbourg, France
[7] Ohio State Univ, Coll Med, Dept Internal Med, Div Med Oncol,Comprehens Canc Ctr, Columbus, OH 43210 USA
[8] St Luc Univ Hosp, Dept Med Oncol, Inst Roi Albert 2, Brussels, Belgium
[9] Univ Hosp 12 Octubre, Med Oncol Dept, Madrid, Spain
[10] Duke Canc Ctr, Durham, NC USA
[11] Univ Ziekenhuizen, Leuven Canc Inst, Leuven, Belgium
[12] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
[13] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA
[14] Univ Colorado, Canc Ctr, Anschutz Med Campus, Aurora, CO USA
[15] Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA
[16] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA
[17] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA
[18] Harvard Med Sch, Massachusetts Gen Hosp, Mass Gen Canc Ctr, Boston, MA 02115 USA
[19] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA
关键词
OPEN-LABEL; SUNITINIB; CANCER; INHIBITOR; SURVIVAL; CRITERIA; THERAPY; MET;
D O I
10.1001/jamaoncol.2021.4544
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This cohort study assesses the clinical activity and toxic effects of cabozantinib to treat brain metastases in patients with metastatic renal cell carcinoma. Question What is the clinical activity and safety of cabozantinib for treatment of brain metastases in patients with renal cell carcinoma? Findings In this cohort study of 88 patients with renal cell carcinoma and brain metastases treated in 15 institutions across 4 countries, the intracranial response rate was 55% in the cohort of patients with progressing brain metastases without concomitant brain-directed local therapy and 47% in the cohort of patients with stable or progressing brain metastases concomitantly treated by brain-directed local therapy. No unexpected toxic effects or neurological adverse events were reported. Meaning These findings show considerable intracranial activity and an acceptable safety profile of cabozantinib in patients with renal cell carcinoma and brain metastases. Importance Patients with brain metastases from renal cell carcinoma (RCC) have been underrepresented in clinical trials, and effective systemic therapy is lacking. Cabozantinib shows robust clinical activity in metastatic RCC, but its effect on brain metastases remains unclear. Objective To assess the clinical activity and toxic effects of cabozantinib to treat brain metastases in patients with metastatic RCC. Design, Setting, and Participants This retrospective cohort study included patients with metastatic RCC and brain metastases treated in 15 international institutions (US, Belgium, France, and Spain) between January 2014 and October 2020. Cohort A comprised patients with progressing brain metastases without concomitant brain-directed local therapy, and cohort B comprised patients with stable or progressing brain metastases concomitantly treated by brain-directed local therapy. Exposures Receipt of cabozantinib monotherapy at any line of treatment. Main Outcomes and Measures Intracranial radiological response rate by modified Response Evaluation Criteria in Solid Tumors, version 1.1, and toxic effects of cabozantinib. Results Of the 88 patients with brain metastases from RCC included in the study, 33 (38%) were in cohort A and 55 (62%) were in cohort B; the majority of patients were men (n = 69; 78%), and the median age at cabozantinib initiation was 61 years (range, 34-81 years). Median follow-up was 17 months (range, 2-74 months). The intracranial response rate was 55% (95% CI, 36%-73%) and 47% (95% CI, 33%-61%) in cohorts A and B, respectively. In cohort A, the extracranial response rate was 48% (95% CI, 31%-66%), median time to treatment failure was 8.9 months (95% CI, 5.9-12.3 months), and median overall survival was 15 months (95% CI, 9.0-30.0 months). In cohort B, the extracranial response rate was 38% (95% CI, 25%-52%), time to treatment failure was 9.7 months (95% CI, 6.0-13.2 months), and median overall survival was 16 months (95% CI, 12.0-21.9 months). Cabozantinib was well tolerated, with no unexpected toxic effects or neurological adverse events reported. No treatment-related deaths were observed. Conclusions and Relevance In this cohort study, cabozantinib showed considerable intracranial activity and an acceptable safety profile in patients with RCC and brain metastases. Support of prospective studies evaluating the efficacy of cabozantinib for brain metastases in patients with RCC is critical.
引用
收藏
页码:1815 / 1823
页数:9
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