Metastatic renal-cell carcinoma (mRCC) treatment relies on anti-angiogenic therapies. Bone metastases occur in nearly 30% of mRCC and can induce symptomatic skeletal-events (SSE) such as pain requiring radiotherapy, pathologic fractures, and spinal cord compression. SSE can be prevented using bone-targeted agents, e.g. bisphosphonates or denosumab. Data about denosumab and anti-angiogenic combination are scarce.
This multicenter retrospective study led by GETUG included mRCC patients (pts) who received anti-angiogenic therapies associated with denosumab from January 2013 to December 2015. The primary endpoint was toxicity related to denosumab, especially osteonecrosis of the jaw (ONJ) and hypocalcaemia.
37 pts were identified and 36 analyzed. The mean age was 60.9 year-old (range 42-81). Twenty-four pts (68%) had an odontological consultation before denosumab introduction and 20 pts (58.3%) had a dental panoramic radiography. Five pts (13.9%) developed an ONJ, among them 3 had a dental extraction while on denosumab treatment. Only one out of the 5 pts has completely recovered from his ONJ. No grade 3-4 hypocalcaemia was reported. SSE occurred in 22 pts (61.1%) including bone pain requiring radiation, clinical fractures, and spinal compression in 22, 3, and 2 pts, respectively.
In this real life population, the incidence of SSE was very high in mRCC pts with bone metastases. The combination of denosumab with anti-angiogenic drugs was associated with a high incidence of ONJ that may have been favored by dental extraction while on treatment. The present study underlines the need to improve strategies to prevent the onset of SSE in this population of pts.
Clinical trial identification
Legal entity responsible for the study
A. Guillot: board PFIZER. S. Negrier: honoraria from Pfizer, Novartis et BMS. D. Pouessel: Board: roche, astellas, Lilly, Novartis, Sanofi Advisory: MSD, AstraZeneca. Speaker : Astellas, Janssen, Boehringer-ingelheim, Sanofi. C. Chevreau: board advisory: Pharmamar Inc, Novartis Inc. L. Albiges: consultaant or advisory role: novartis, pfizer, amgen, BMS, Bayer, Sanofi, Cerulean. K. Fizazi: consultant/advisor for Amgen Inc.,Novartis,Clovis, Pfizer, CSL, Behring, and Bayer- GlaxoSmithKline, and Genentech- speakers' bureau for Genomic Health research funding from Amgen Inc., Novartis, Bayer, and Puma. All other authors have declared no conflicts of interest.