Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With Metastatic Renal Cell Carcinoma: A GETUG Study - Université de Montpellier
Article Dans Une Revue Clinical Genitourinary Cancer Année : 2019

Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With Metastatic Renal Cell Carcinoma: A GETUG Study

Hakim Mahammedi
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Guilhem Roubaud
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Gwénaelle Gravis
Sophie Tartas
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Stéphane Culine

Résumé

BACKGROUND: About one-third of patients with renal cell carcinoma (RCC) have detectable metastases at diagnosis. Among them, bone is the second most frequent metastatic site. Treatment of metastatic RCC mostly relies on anti-angiogenic (AA) therapies and, more recently, immunotherapy. Skeletal-related events (SREs) can be prevented with bone-targeted therapies such as denosumab (Dmab), which has demonstrated superiority when compared with zoledronic acid in solid tumors. However, there is limited available data on Dmab toxicity in combination with AA therapies in patients with kidney cancer. The objective of this study was to retrospectively analyze the toxicity profile (mainly osteonecrosis of the jaw [ONJ] and hypocalcemia) in patients with metastatic renal cell carcinoma (mRCC) treated with Dmab and AA therapy combination. PATIENTS AND METHODS: We conducted a multicenter retrospective study among centers from the French Groupe d'Etudes des Tumeurs Uro Genitales (GETUG). Patients with bone metastases who received concurrently or sequentially AA therapy and Dmab were included in this study. RESULTS: A total of 41 patients with mRCC were enrolled. Although no patient presented with severe hypocalcemia, ONJ occurred in 7 (17%) of 41 patients. Interestingly, all patients with ONJ received the Dmab and AA combination in the first line of treatment; among these patients, 3 patients had no risk factor other than the Dmab and AA combination. CONCLUSION: The incidence of ONJ was high in this real-life population of patients with mRCC treated with AA therapies combined with Dmab. This toxicity signal should warn physicians about this combination in the mRCC population.
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Dates et versions

hal-02420071 , version 1 (19-12-2019)

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Aline Guillot, Charlotte Joly, Philippe Barthélémy, Emeline Meriaux, Sylvie Négrier, et al.. Denosumab Toxicity When Combined With Anti-angiogenic Therapies on Patients With Metastatic Renal Cell Carcinoma: A GETUG Study. Clinical Genitourinary Cancer, 2019, 17 (1), pp.e38-e43. ⟨10.1016/j.clgc.2018.08.006⟩. ⟨hal-02420071⟩
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