Laure Hirsch1,2, Nieves Martinez Chanza1,3, Subrina Farah4, Wanling Xie4, Ronan Flippot2, David A Braun1, Nityam Rathi5, Jonathan Thouvenin6, Katharine A Collier7, Emmanuel Seront8, Guillermo de Velasco9, Hannah Dzimitrowicz10, Benoit Beuselinck11, Wenxin Xu1,12, I Alex Bowman13, Elaine T Lam14, Bashar Abuqayas15, Mehmet Asim Bilen16, Andreas Varkaris12, Yousef Zakharia15, Michael R Harrison10, Amir Mortazavi7, Philippe Barthélémy6, Neeraj Agarwal5, Rana R McKay17, Priscilla K Brastianos18, Katherine M Krajewski19, Laurence Albigès2, Lauren C Harshman1, Toni K Choueiri1. 1. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 2. Department of Medical Oncology, Gustave Roussy, Villejuif, France. 3. Medical Oncology Department, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium. 4. Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts. 5. Huntsman Cancer Institute, Salt Lake City, Utah. 6. Department of Medical Oncology, Institut de Cancérologie Strasbourg Europe, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France. 7. Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus. 8. Institut Roi Albert II, Department of Medical Oncology, St Luc University Hospital, Brussels, Belgium. 9. Medical Oncology Department, University Hospital 12 de Octubre, Madrid, Spain. 10. Duke Cancer Center, Durham, North Carolina. 11. Leuven Cancer Institute, Universitaire Ziekenhuizen, Leuven, Belgium. 12. Beth Israel Deaconess Medical Center, Boston, Massachusetts. 13. University of Texas Southwestern Medical Center, Dallas. 14. University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora. 15. Holden Comprehensive Cancer Center, University of Iowa, Iowa City. 16. Winship Cancer Institute, Emory University, Atlanta, Georgia. 17. Moores Cancer Center, University of California San Diego, La Jolla. 18. Mass General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston. 19. Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts.
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.
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.
Authors: Jacob J Adashek; Joshua J Breunig; Edwin Posadas; Neil A Bhowmick; Leigh Ellis; Stephen J Freedland; Hyung Kim; Robert Figlin; Jun Gong Journal: Drugs Date: 2022-02-17 Impact factor: 9.546
Authors: Stefanie D Krens; Nielka P van Erp; Stefanie L Groenland; Dirk Jan A R Moes; Sasja F Mulder; Ingrid M E Desar; Tom van der Hulle; Neeltje Steeghs; Carla M L van Herpen Journal: BMC Cancer Date: 2022-03-02 Impact factor: 4.430