PMID- 31178240 OWN - NLM STAT- MEDLINE DCOM- 20200416 LR - 20200416 IS - 1938-0682 (Electronic) IS - 1558-7673 (Linking) VI - 17 IP - 4 DP - 2019 Aug TI - Cabozantinib in Renal Cell Carcinoma With Brain Metastases: Safety and Efficacy in a Real-World Population. PG - 291-298 LID - S1558-7673(18)30652-9 [pii] LID - 10.1016/j.clgc.2019.05.002 [doi] AB - 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. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Peverelli, Giorgia AU - Peverelli G AD - Medical Oncology Department, Genitourinary Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. FAU - Raimondi, Alessandra AU - Raimondi A AD - Medical Oncology Department, Genitourinary Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. FAU - Ratta, Raffaele AU - Ratta R AD - Medical Oncology Department, Genitourinary Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. FAU - Verzoni, Elena AU - Verzoni E AD - Medical Oncology Department, Genitourinary Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. FAU - Bregni, Marco AU - Bregni M AD - Ospedale di Circolo di Busto Arsizio, Busto Arsizio, Italy. FAU - Cortesi, Enrico AU - Cortesi E AD - Department of Medical Oncology B, Policlinico Umberto I "Sapienza" University of Rome, Rome, Italy. FAU - Carteni, Giacomo AU - Carteni G AD - Oncology Unit, Antonio Cardarelli Hospital, Naples, Italy. FAU - Fornarini, Giuseppe AU - Fornarini G AD - IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Medical Oncology Department, Genova, Italy. FAU - Facchini, Gaetano AU - Facchini G AD - Departmental Unit of Experimental Uro-Andrological Clinical Oncology, Department of Uro-Gynaecological Oncology, National Cancer Institute -IRCCS- G. Pascale Foundation, Naples, Italy. FAU - Buti, Sebastiano AU - Buti S AD - Medical Oncology Unit, University Hospital of Parma, Parma, Italy. FAU - Galli, Luca AU - Galli L AD - Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy. FAU - Tucci, Marcello AU - Tucci M AD - Division of Medical Oncology, San Luigi Gonzaga Hospital, Department of Oncology, University of Turin, Orbassano, Turin, Italy. FAU - Prisciandaro, Michele AU - Prisciandaro M AD - Medical Oncology Department, Genitourinary Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. FAU - Procopio, Giuseppe AU - Procopio G AD - Medical Oncology Department, Genitourinary Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. Electronic address: giuseppe.procopio@istitutotumori.mi.it. LA - eng PT - Journal Article DEP - 20190513 PL - United States TA - Clin Genitourin Cancer JT - Clinical genitourinary cancer JID - 101260955 RN - 0 (Anilides) RN - 0 (Pyridines) RN - 1C39JW444G (cabozantinib) SB - IM MH - Administration, Oral MH - Anilides/*administration & dosage/adverse effects MH - Brain Neoplasms/*drug therapy/*secondary MH - Carcinoma, Renal Cell/*drug therapy MH - Disease-Free Survival MH - Female MH - Humans MH - Kidney Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Pyridines/*administration & dosage/adverse effects MH - Retrospective Studies MH - Treatment Outcome OTO - NOTNLM OT - Brain-specific response OT - Metastatic renal cell carcinoma OT - Neurological toxicity OT - Systemic and loco-regional treatment integration OT - Tyrosine kinase inhibitors EDAT- 2019/06/11 06:00 MHDA- 2020/04/17 06:00 CRDT- 2019/06/11 06:00 PHST- 2018/08/29 00:00 [received] PHST- 2019/02/26 00:00 [revised] PHST- 2019/05/03 00:00 [accepted] PHST- 2019/06/11 06:00 [pubmed] PHST- 2020/04/17 06:00 [medline] PHST- 2019/06/11 06:00 [entrez] AID - S1558-7673(18)30652-9 [pii] AID - 10.1016/j.clgc.2019.05.002 [doi] PST - ppublish SO - Clin Genitourin Cancer. 2019 Aug;17(4):291-298. doi: 10.1016/j.clgc.2019.05.002. Epub 2019 May 13.