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

Authors :
Hannah Dzimitrowicz
Wenxin Xu
I. Alex Bowman
Neeraj Agarwal
Nieves Martinez Chanza
Mehmet Asim Bilen
Amir Mortazavi
Emmanuel Seront
Rana R. McKay
Katharine Collier
Ronan Flippot
Guillermo Velasco
Philippe Barthélémy
Laurence Albiges
Wanling Xie
David A. Braun
Priscilla K. Brastianos
Katherine M. Krajewski
Nityam Rathi
Subrina Farah
Lauren C. Harshman
Toni K. Choueiri
Michael R. Harrison
Andreas Varkaris
Bashar Abuqayas
Jonathan Thouvenin
Yousef Zakharia
Laure Hirsch
Elaine T. Lam
Benoit Beuselinck
Source :
JAMA Oncology. 7:1815
Publication Year :
2021
Publisher :
American Medical Association (AMA), 2021.

Abstract

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.

Details

ISSN :
23742437
Volume :
7
Database :
OpenAIRE
Journal :
JAMA Oncology
Accession number :
edsair.doi.dedup.....bf2c91618b988f3b01700b880bc60b96
Full Text :
https://doi.org/10.1001/jamaoncol.2021.4544