Temsirolimus versus Pazopanib (TemPa) in Patients with Advanced Clear-cell Renal Cell Carcinoma and Poor-risk Features: A Randomized Phase II Trial

Eur Urol Oncol. 2020 Oct;3(5):687-694. doi: 10.1016/j.euo.2019.06.004. Epub 2019 Jul 2.


Background: Temsirolimus has level 1 evidence for initial treatment of poor-risk patients with advanced renal cell carcinoma (mRCC), but its efficacy has not been directly compared with an antiangiogenic tyrosine kinase inhibitor (vascular endothelial growth factor receptor tyrosine kinase inhibitor [VEGFR TKi]) in this setting.

Objective: To evaluate temsirolimus versus pazopanib as first-line therapy in patients with mRCC, predominant clear-cell features, and clinical characteristics of a poor prognosis.

Design, setting, and participants: A randomized (1:1) phase II trial in 69 treatment-naïve mRCC patients and with three or more predictors of short survival for temsirolimus was conducted during 2012-2017 in a single academic cancer center. Crossover to the alternative treatment upon discontinuation of the first-line agent was permitted.

Intervention: Mechanistic target of rapamycin inhibitor temsirolimus and VEGFR TKi pazopanib.

Outcome measurements and statistical analysis: The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), safety, and patient-reported outcomes (PROs). Radiographic response was assessed by blinded radiologists. Efficacy outcomes were adjusted by prior nephrectomy status, prior interleukin-2 treatment, and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score.

Results and limitations: Thirty-five patients received temsirolimus and 34 received pazopanib upfront; 72% overall had poor risk by IMDC. Median PFS in the first line was 2.7mo with temsirolimus and 5.2mo with pazopanib (adjusted hazard ratio [HR] 1.36, 95% confidence interval [CI] 0.84-2.22; p=0.210). Median OS was 7.1mo with temsirolimus and 11.9mo with pazopanib (adjusted HR 1.16, 95% CI 0.70-1.93; p=0.558), and ORRs were 5.9% and 21.2%, respectively (adjusted odds ratio 5.2, 95% CI 0.9-29.3; p=0.062). PRO measures favored pazopanib. Five patients discontinued first-line therapy due to adverse events.

Conclusions: Temsirolimus and pazopanib had modest activity in patients with poor-risk clear-cell mRCC, and therefore their use should be discouraged in this setting.

Patient summary: We evaluated outcomes of advanced renal cell carcinoma patients presenting with aggressive features when treated with temsirolimus or pazopanib as first-line therapy. Survival was <1yr for most, suggesting that more efficacious alternative treatments should be favored for these patients.

Keywords: Cytokines and angiogenic factors; First line; International Metastatic Renal Cell Carcinoma Database Consortium risk groups; Pazopanib; Poor-risk metastatic renal cell carcinoma; Temsirolimus.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Female
  • Humans
  • Indazoles / therapeutic use*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Pyrimidines / therapeutic use*
  • Risk Assessment
  • Single-Blind Method
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Sulfonamides / therapeutic use*


  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • temsirolimus
  • pazopanib
  • Sirolimus