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.
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.
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.
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.
Clinical genitourinary cancer. 2018 Sep 06 [Epub ahead of print]
Aline Guillot, Charlotte Joly, Philippe Barthélémy, Emeline Meriaux, Sylvie Negrier, Damien Pouessel, Christine Chevreau, Hakim Mahammedi, Nadine Houede, Guilhem Roubaud, Gwenaelle Gravis, Sophie Tartas, Laurence Albiges, Cécile Vassal, Mathieu Oriol, Fabien Tinquaut, Sophie Espenel, Wafa Bouleftour, Stéphane Culine, Karim Fizazi
Department of Medical Oncology, Institut de cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France., Hôpital Henri Mondor, APHP, Créteil, France., Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Centre François Baclesse, Caen, France., Centre Léon Bérard, Lyon, France., Hôpital Saint-Louis, AP-HP, Paris, France., IUCT Oncopole, Toulouse France Centre Jean Perrin, France., Centre Jean-Perrin, Medical Oncology, Clermont-Ferrand, France., Institut de Cancérologie du Gard, Nîmes, France., Institut Bergonié, Bordeaux, France., Institut Paoli Calmette, Marseille, France., Hôpitaux Universitaires de Lyon, Lyon, France., Institut Gustave Roussy, Villejuif, France., Department of Biostatistics, Institut de Cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France., Department of Radiotherapy, Institut de Cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France., Department of Medical Oncology, Institut de cancérologie Lucien Neuwirth, Saint-Priest-en-Jarez, France. Electronic address: .