Advertisement
Original Study| Volume 17, ISSUE 4, P291-298, August 2019

Cabozantinib in Renal Cell Carcinoma With Brain Metastases: Safety and Efficacy in a Real-World Population

      Abstract

      Background

      Cabozantinib showed efficacy and manageable toxicity in patients with metastatic renal cell carcinoma (mRCC). In this study we aimed to describe the safety and to collect evidence on the potential efficacy of cabozantinib in mRCC patients with brain metastases (BM) in a real-world experience.

      Materials and Methods

      We retrospectively collected data of patients treated with cabozantinib within the Italian Managed Access Program. Patients were selected for the presence of BM before the start of treatment and for at least 1 previous tyrosine kinase inhibitor (TKI) treatment regimen for metastatic disease. Safety data were reported, and overall response rate (ORR), brain-specific response, progression-free survival (PFS), and median overall survival (OS) were analyzed.

      Results

      Overall, 12 patients treated with cabozantinib were evaluated. Any grade adverse events (AEs) accounted for 92%, Grade 3/4 AEs rated at 36% with no major neurological side effects. The most common AEs included hypertension (33%), fatigue (24%), aminotransferase elevation (25%), hypothyroidism (16%), and gastrointestinal toxicity (16%). The ORR was 50% with a disease control rate of 75%. All 5 patients treated with a combined systemic and brain-directed approach obtained intracranial disease control, without increased toxicity. Median PFS and median OS were 5.8 and 8.8 months, respectively. Comparable safety and tolerability results for other TKI regimens were reported from the literature.

      Conclusion

      Cabozantinib showed safety, acceptable tolerability, and promising antitumor activity in a population of mRCC patients with BM from a real-world experience. A combined modality approach for renal cell carcinoma with BM, whenever feasible, could be recommended to improve oncological outcomes.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Capitanio U.
        • Montorsi F.
        Renal cancer.
        Lancet. 2016; 387: 894-906
        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2019.
        CA Cancer J Clin. 2019; 69: 7-34
        • Ferlay J.S.I.
        • Ervik M.
        • Dikshit R.
        • et al.
        GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11.
        (Available at:) (Accessed: February 19, 2019)
        • Mennitto A.
        • Verzoni E.
        • Calareso G.
        • et al.
        Treatment of advanced renal cell carcinoma: recent advances and current role of immunotherapy, surgery, and cryotherapy.
        Tumori J. 2016; 103: 15-21
        • Motzer R.J.
        • Hutson T.E.
        • Tomczak P.
        • et al.
        Sunitinib versus interferon-alfa in metastatic renal-cell carcinoma.
        N Engl J Med. 2007; 356: 115-124
        • Escudier B.
        • Eisen T.
        • Stadler W.M.
        • et al.
        Sorafenib in advanced clear-cell renal-cell carcinoma.
        N Engl J Med. 2007; 356: 125-134
        • Motzer R.J.
        • Hutson T.E.
        • Cella D.
        • et al.
        Pazopanib versus sunitinib in metastatic renal-cell carcinoma.
        N Engl J Med. 2013; 369: 722-731
        • Rini B.I.
        • Escudier B.
        • Tomczak P.
        • et al.
        Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.
        Lancet. 2011; 378: 1931-1939
        • Motzer R.J.
        • Nosov D.
        • Eisen T.
        • et al.
        Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial.
        J Clin Oncol. 2013; 31: 3791-3799
        • Grassi P.
        • Verzoni E.
        • Ratta R.
        • et al.
        Cabozantinib in the treatment of advanced renal cell carcinoma: design, development, and potential place in the therapy.
        Drug Des Devel Ther. 2016; 10: 2167-2172
        • Choueiri T.K.
        • Escudier B.
        • Powles T.
        • et al.
        Cabozantinib versus everolimus in advanced renal-cell carcinoma.
        N Engl J Med. 2015; 373: 1814-1823
        • Choueiri T.K.
        • Escudier B.
        • Powles T.
        • et al.
        Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial.
        Lancet Oncol. 2016; 17: 917-927
        • Choueiri T.K.
        • Halabi S.
        • Sanford B.L.
        • et al.
        Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the Alliance A031203 CABOSUN trial.
        J Clin Oncol. 2017; 35: 591-597
        • Bennani O.
        • Derrey S.
        • Langlois O.
        • et al.
        Brain metastasis from renal cell carcinoma.
        Neurochirurgie. 2014; 60: 12-16
        • Vickers M.M.
        • Al-Harbi H.
        • Choueiri T.K.
        • et al.
        Prognostic factors of survival for patients with metastatic renal cell carcinoma with brain metastases treated with targeted therapy: results from the International Metastatic Renal Cell Carcinoma Database Consortium.
        Clin Genitourin Cancer. 2013; 11: 311-315
        • Choi S.Y.
        • Yoo S.
        • You D.
        • et al.
        Prognostic factors for survival of patients with synchronous or metachronous brain metastasis of renal cell carcinoma.
        Clin Genitourin Cancer. 2017; 15: 717-723
        • Sperduto P.W.
        • Deegan B.J.
        • Li J.
        • et al.
        Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool.
        Neuro Onco. 2018; 20: 1652-1660
        • Culine S.
        • Bekradda M.
        • Kramar A.
        • et al.
        Prognostic factors for survival in patients with brain metastases from renal cell carcinoma.
        Cancer. 1998; 83: 2548-2553
        • Ratta R.
        • Verzoni E.
        • Di Maio M.
        • et al.
        Exposure to multiple lines of treatment and survival of patients with metastatic renal cell carcinoma: a real-world analysis.
        Clin Genitourin Cancer. 2018; 16: e735-e742
        • Staehler M.
        • Haseke N.
        • Nuhn P.
        • et al.
        Simultaneous anti-angiogenic therapy and single-fraction radiosurgery in clinically relevant metastases from renal cell carcinoma.
        BJU Int. 2011; 108: 673-678
        • Dudek A.Z.
        • Raza A.
        • Chi M.
        • et al.
        Brain metastases from renal cell carcinoma in the era of tyrosine kinase inhibitors.
        Clin Genitourin Cancer. 2013; 11: 155-160
        • Gore M.E.
        • Szczylik C.
        • Porta C.
        • et al.
        Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial.
        Lancet Oncol. 2009; 10: 757-763
        • Gore M.E.
        • Szczylik C.
        • Porta C.
        • et al.
        Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma.
        Br J Cancer. 2015; 113: 12-19
        • Gore M.E.
        • Hariharan S.
        • Porta C.
        • et al.
        Sunitinib in metastatic renal cell carcinoma patients with brain metastases.
        Cancer. 2011; 117: 501-509
        • Stadler W.M.
        • Figlin R.A.
        • McDermott D.F.
        • et al.
        Safety and efficacy results of the advanced renal cell carcinoma sorafenib Expanded Access Program in North America.
        Cancer. 2010; 116: 1272-1280
        • Beck J.
        • Procopio G.
        • Bajetta E.
        • et al.
        Final results of the European advanced renal cell carcinoma sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings.
        Ann Oncol. 2011; 22: 1812-1823
        • Klempner S.J.
        • Borghei A.
        • Hakimian B.
        • et al.
        Intracranial activity of cabozantinib in MET exon 14–positive NSCLC with brain metastases.
        J Thorac Oncol. 2016; 12: 152-156
        • Négrier S.
        • Moriceau G.
        • Attignon V.
        • et al.
        Activity of cabozantinib in radioresistant brain metastases from renal cell carcinoma: two case reports.
        J Med Case Rep. 2018; 25: 351
        • Derosa L.
        • Le Teuff G.
        • Khordahi M.
        • et al.
        Inter and intra-tumor heterogeneity of PD-L1 and MET expression in metastatic renal cell carcinoma (mRCC).
        J Clin Oncol. 2017; 35: 4569
      1. De Liano AG, Venugopal B, Fife K, et al. Cabozantinib in metastatic renal cell carcinoma (mRCC): Real world experience from the UK. J Clin Oncol 36 (15 suppl).

        • Ciccarese C.
        • Iacovelli R.
        • Mosillo C.
        • et al.
        Exceptional response to cabozantinib of rapidly evolving brain metastases of renal cell carcinoma: a case report and review of the literature.
        Clin Genitourin Cancer. 2018; 16: e1069-e1071
        • Juloori A.
        • Miller J.A.
        • Parsai S.
        • et al.
        Overall survival and response to radiation and targeted therapies among patients with renal cell carcinoma brain metastases.
        J Neurosurg. 2019; 18: 1-9
        • Bassanelli M.
        • Viterbo A.
        • Roberto M.
        • et al.
        Multimodality treatment of brain metastasis from renal cell carcinoma in the era of targeted therapy.
        Ther Adv Med Oncol. 2017; 9: 217
        • Bastos D.A.
        • Molina A.M.
        • Hatzoglou V.
        • et al.
        Safety and efficacy of targeted therapy for renal cell carcinoma with brain metastasis.
        Clin Genitourin Cancer. 2015; 13: 59-66
        • Tallet A.V.
        • Dhermain F.
        • Le Rhun E.
        • et al.
        Combined irradiation and targeted therapy or immune checkpoint blockade in brain metastases: toxicities and efficacy.
        Ann Oncol. 2017; 28: 2962-2976
        • Langrand-Escure J.
        • Vallard A.
        • Rivoirard R.
        • et al.
        Safety assessment of molecular targeted therapies in association with radiotherapy in metastatic renal cell carcinoma: a real-life report.
        Anticancer Drugs. 2016; 27: 427-432
        • Procopio G.
        • Prisciandaro M.
        • Iacovelli R.
        • et al.
        Safety and efficacy of cabozantinib in metastatic renal-cell carcinoma: real-world data from an Italian Managed Access Program.
        Clin Genitourin Cancer. 2018; 16: e945-e951
        • National Cancer Institute
        Common Terminology Criteria for Adverse Events (CTCAE) v.4.
        (Available at:) (Accessed: February 19, 2019)
        • Eisenhauer E.A.
        • Therasse P.
        • Bogaerts J.
        • et al.
        New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1).
        Eur J Cancer. 2009; 45: 228-247
        • Chevreau C.
        • Ravaud A.
        • Escudier B.
        • et al.
        A phase II trial of sunitinib in patients with renal cell cancer and untreated brain metastases.
        Clin Genitourin Cancer. 2014; 12: 50-54
        • Du Y.
        • Pahernik S.
        • Hadaschik B.
        • et al.
        Impact of resection and systemic therapy on the survival of patients with brain metastasis of metastatic renal cell carcinoma.
        J Neuro Oncol. 2016; 130: 221-228