Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma

Cancer. 2015 Oct 1;121(19):3435-43. doi: 10.1002/cncr.29503. Epub 2015 Jun 8.


Background: Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.

Methods: This was a phase 2, single-arm trial of sunitinib and gemcitabine in patients with sarcomatoid or poor-risk RCC. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the time to progression (TTP), overall survival (OS), safety, and biomarker correlatives.

Results: Overall, 39 patients had sarcomatoid RCC, and 33 had poor-risk RCC. The ORR was 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk RCC. The median TTP and OS for patients with sarcomatoid RCC were 5 and 10 months, respectively. For patients with poor-risk disease, the median TTP and OS were 5.5 and 15 months, respectively. Patients whose tumors had >10% sarcomatoid histology had a higher clinical benefit rate (ORR plus stable disease) than those with ≤10% sarcomatoid histology (P = .04). The most common grade 3 or higher treatment-related adverse events included neutropenia (n = 20), anemia (n = 10), and fatigue (n = 7).

Conclusions: These results suggest that antiangiogenic therapy and cytotoxic chemotherapy are an active and well-tolerated combination for patients with aggressive RCC. The combination may be more efficacious than either therapy alone and is currently under further investigation.

Keywords: chemotherapy; poor risk; renal cell carcinoma; sarcomatoid; targeted; vascular endothelial growth factor (VEGF).

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pyrroles / therapeutic use*
  • Sunitinib


  • Indoles
  • Pyrroles
  • Deoxycytidine
  • gemcitabine
  • Sunitinib