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Clinical Activity and Safety of Cabozantinib for Brain Metastases in Patients With Renal Cell Carcinoma
- 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.
- Subjects :
- Male
Oncology
Cancer Research
medicine.medical_specialty
Cabozantinib
Pyridines
Cohort Studies
chemistry.chemical_compound
Renal cell carcinoma
Internal medicine
medicine
Humans
Anilides
Prospective Studies
Prospective cohort study
Carcinoma, Renal Cell
Retrospective Studies
Brain Neoplasms
business.industry
Retrospective cohort study
medicine.disease
Kidney Neoplasms
chemistry
Response Evaluation Criteria in Solid Tumors
Concomitant
Cohort
Female
business
Cohort study
Subjects
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