title: Bone metastases affect prognosis but not effectiveness of third-line targeted therapies in patients with metastatic renal cell carcinoma.
abstract: BACKGROUND
  Treatment of metastatic renal cell carcinoma (mRCC) has improved with the use of targeted therapies, but bone metastases continue to be negative prognostic factor.
  
  
  METHODS
  Patients with mRCC treated with everolimus (EV) or sorafenib (SO) after two previous lines of targeted therapies were included in the analysis. Overall survival (OS) and progression-free survival (PFS) were assessed based on the presence of bone metastases and type of therapy; they were also adjusted based on prognostic criteria.
  
  
  RESULTS
  Of the 233 patients with mRCC, 76 had bone metastases. Of the 233 patients, EV and SO were administered in 143 and 90 patients, respectively. Median OS was 10.4 months in patients with BMs and 17.4 months in patients without bone metastases (p = 0.002). EV decreased the risk of death by 18% compared to SO (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.74-0.91; p < 0.001), with comparable effects in patients with or without bone metastases. In the same manner, EV decreased the risk of progression by 12% compared to SO (adjusted HR 0.88, 95% CI 0.82-0.96; p = 0.002), but this difference was not significant in patients without bone metastases. The major limitations of the study are its retrospective nature, the heterogeneity of the methods to detect bone metastases, and the lack of data about patients treated with bisphosphonates.
  
  
  CONCLUSIONS
  The relative benefit of targeted therapies in mRCC is not affected by the presence of bone metastases, but patients without bone metastases have longer response to therapy and overall survival.
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Roberto
authors: R
authors: Iacovelli
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Daniele
authors: D
authors: Santini
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Mimma
authors: M
authors: Rizzo
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Alessandra
authors: A
authors: Felici
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Matteo
authors: M
authors: Santoni
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Elena
authors: E
authors: Verzoni
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Cristina
authors: C
authors: Masini
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Francesco
authors: F
authors: Massari
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Nicola
authors: N
authors: Calvani
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Rome, Italy;
authors: Alessandra
authors: A
authors: Mosca
authors: Fondazione IRCCS Istituto Nazionale Tumori, Division of Medical Oncology, Rome, Italy.
authors: Giuseppe
authors: G
authors: Procopio