A population-based overview of sequences of targeted therapy in metastatic renal cell carcinoma

Clin Genitourin Cancer. 2014 Aug;12(4):e127-31. doi: 10.1016/j.clgc.2013.12.003. Epub 2013 Dec 27.


Background: Several TTs are available to treat mRCC; however, the optimal sequence of therapy remains unknown.

Patients and methods: Consecutive population-based samples of patients with mRCC treated with TT were collected from 12 cancer centers via the International Metastatic Renal Cell Carcinoma Database Consortium. Patient characteristics, first-line and second-line progression-free survival rates and overall survival data were collected based on sequencing of TT. Multivariable analysis was performed when there were significant differences on univariable analysis.

Results: A total of 2106 patients were included with a median follow-up of 36 months; 907 (43%) and 318 (15%) patients received subsequent second-line and third-line TT, respectively. Baseline characteristics were well matched among different sequences apart from more patients with non-clear-cell histology in the vascular endothelial growth factor (VEGF) to mammalian target of rapamycin (mTOR) group compared with the VEGF to VEGF group sequence. When adjusting for the Heng risk criteria and non-clear-cell histology, the hazard ratio for death for the VEGF to mTOR group versus the VEGF to VEGF group was 0.833 (95% confidence interval [CI], 0.669-1.037; P = .1016). More specifically, the adjusted hazard ratio for death for the sunitinib to everolimus versus sunitinib to temsirolimus sequences was 0.774 (95% CI, 0.52-1.153; P = .2086).

Conclusion: In this large multicenter analysis evaluating different sequences of TT in mRCC, no substantial effect on outcome based on sequence of TT was identified.

Keywords: Kidney cancer; Mammalian target of rapamycin; Sequencing; Treatment; Vascular endothelial growth factor.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • Female
  • Follow-Up Studies
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy*
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*


  • Antineoplastic Agents
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MTOR protein, human
  • TOR Serine-Threonine Kinases