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

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. Cancer 2015;121:3435–43. © 2015 American Cancer Society. This study demonstrates that multimodality therapy with gemcitabine and sunitinib is feasible and is associated with objective responses in patients with sarcomatoid or poor‐risk renal cell carcinoma. The results of this study are currently being validated in a randomized phase 2 trial of sunitinib with or without gemcitabine for advanced sarcomatoid renal cell carcinoma (NCT01164228).