Cabozantinib in Renal Cell Carcinoma With Brain Metastases

Giorgia Peverelli, Alessandra Raimondi, Raffaele Ratta, Elena Verzoni, Marco Bregni, Enrico Cortesi, Giacomo Cartenì, Giuseppe Fornarini, Gaetano Facchini, Sebastiano Buti, Luca Galli, Marcello Tucci, Michele Prisciandaro, Giuseppe Procopio

Research output: Contribution to journalArticle

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.
Original languageEnglish
JournalClinical Genitourinary Cancer
DOIs
Publication statusPublished - 2019

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Renal Cell Carcinoma
Neoplasm Metastasis
Brain
Safety
Protein-Tyrosine Kinases
Disease-Free Survival
Survival
Hypothyroidism
Transaminases
cabozantinib
Fatigue
Hypertension
Therapeutics
Population

Keywords

  • Brain-specific response
  • Metastatic renal cell carcinoma
  • Neurological toxicity
  • Systemic and loco-regional treatment integration
  • Tyrosine kinase inhibitors

Cite this

Peverelli, G., Raimondi, A., Ratta, R., Verzoni, E., Bregni, M., Cortesi, E., ... Procopio, G. (2019). Cabozantinib in Renal Cell Carcinoma With Brain Metastases. Clinical Genitourinary Cancer. https://doi.org/10.1016/j.clgc.2019.05.002

Cabozantinib in Renal Cell Carcinoma With Brain Metastases. / Peverelli, Giorgia; Raimondi, Alessandra; Ratta, Raffaele; Verzoni, Elena; Bregni, Marco; Cortesi, Enrico; Cartenì, Giacomo; Fornarini, Giuseppe; Facchini, Gaetano; Buti, Sebastiano; Galli, Luca; Tucci, Marcello; Prisciandaro, Michele; Procopio, Giuseppe.

In: Clinical Genitourinary Cancer, 2019.

Research output: Contribution to journalArticle

Peverelli, G, Raimondi, A, Ratta, R, Verzoni, E, Bregni, M, Cortesi, E, Cartenì, G, Fornarini, G, Facchini, G, Buti, S, Galli, L, Tucci, M, Prisciandaro, M & Procopio, G 2019, 'Cabozantinib in Renal Cell Carcinoma With Brain Metastases', Clinical Genitourinary Cancer. https://doi.org/10.1016/j.clgc.2019.05.002
Peverelli, Giorgia ; Raimondi, Alessandra ; Ratta, Raffaele ; Verzoni, Elena ; Bregni, Marco ; Cortesi, Enrico ; Cartenì, Giacomo ; Fornarini, Giuseppe ; Facchini, Gaetano ; Buti, Sebastiano ; Galli, Luca ; Tucci, Marcello ; Prisciandaro, Michele ; Procopio, Giuseppe. / Cabozantinib in Renal Cell Carcinoma With Brain Metastases. In: Clinical Genitourinary Cancer. 2019.
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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.",
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author = "Giorgia Peverelli and Alessandra Raimondi and Raffaele Ratta and Elena Verzoni and Marco Bregni and Enrico Cortesi and Giacomo Carten{\`i} and Giuseppe Fornarini and Gaetano Facchini and Sebastiano Buti and Luca Galli and Marcello Tucci and Michele Prisciandaro and Giuseppe Procopio",
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T1 - Cabozantinib in Renal Cell Carcinoma With Brain Metastases

AU - Peverelli, Giorgia

AU - Raimondi, Alessandra

AU - Ratta, Raffaele

AU - Verzoni, Elena

AU - Bregni, Marco

AU - Cortesi, Enrico

AU - Cartenì, Giacomo

AU - Fornarini, Giuseppe

AU - Facchini, Gaetano

AU - Buti, Sebastiano

AU - Galli, Luca

AU - Tucci, Marcello

AU - Prisciandaro, Michele

AU - Procopio, Giuseppe

PY - 2019

Y1 - 2019

N2 - 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.

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.

KW - Brain-specific response

KW - Metastatic renal cell carcinoma

KW - Neurological toxicity

KW - Systemic and loco-regional treatment integration

KW - Tyrosine kinase inhibitors

U2 - 10.1016/j.clgc.2019.05.002

DO - 10.1016/j.clgc.2019.05.002

M3 - Article

JO - Clinical Genitourinary Cancer

JF - Clinical Genitourinary Cancer

SN - 1558-7673

ER -