Giorgia Peverelli1, Alessandra Raimondi1, Raffaele Ratta1, Elena Verzoni1, Marco Bregni2, Enrico Cortesi3, Giacomo Cartenì4, Giuseppe Fornarini5, Gaetano Facchini6, Sebastiano Buti7, Luca Galli8, Marcello Tucci9, Michele Prisciandaro1, Giuseppe Procopio10. 1. Medical Oncology Department, Genitourinary Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. 2. Ospedale di Circolo di Busto Arsizio, Busto Arsizio, Italy. 3. Department of Medical Oncology B, Policlinico Umberto I "Sapienza" University of Rome, Rome, Italy. 4. Oncology Unit, Antonio Cardarelli Hospital, Naples, Italy. 5. IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Medical Oncology Department, Genova, Italy. 6. Departmental Unit of Experimental Uro-Andrological Clinical Oncology, Department of Uro-Gynaecological Oncology, National Cancer Institute -IRCCS- G. Pascale Foundation, Naples, Italy. 7. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 8. Medical Oncology Unit, Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy. 9. Division of Medical Oncology, San Luigi Gonzaga Hospital, Department of Oncology, University of Turin, Orbassano, Turin, Italy. 10. Medical Oncology Department, Genitourinary Cancer Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. Electronic address: giuseppe.procopio@istitutotumori.mi.it.
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.
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.
Authors: Björn Scheffler; Sied Kebir; Martin Glas; Lazaros Lazaridis; Teresa Schmidt; Christoph Oster; Tobias Blau; Daniela Pierscianek; Jens T Siveke; Sebastian Bauer; Hans-Ulrich Schildhaus; Ulrich Sure; Kathy Keyvani; Christoph Kleinschnitz; Martin Stuschke; Ken Herrmann; Cornelius Deuschl Journal: J Cancer Res Clin Oncol Date: 2022-08-12 Impact factor: 4.322
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
Authors: Marco Stellato; Daniele Santini; Elena Verzoni; Ugo De Giorgi; Francesco Pantano; Chiara Casadei; Giuseppe Fornarini; Marco Maruzzo; Andrea Sbrana; Giuseppe Di Lorenzo; Mariella Soraru; Emanuele Naglieri; Sebastiano Buti; Rocco De Vivo; Andrea Napolitano; Francesca Vignani; Claudia Mucciarini; Francesco Grillone; Giandomenico Roviello; Marilena Di Napoli; Giuseppe Procopio Journal: Front Oncol Date: 2021-06-08 Impact factor: 6.244