Gemcitabine-Sunitinib Combo Active in Aggressive RCC

Patients with sarcomatoid or poor-risk renal cell carcinoma (RCC) had frequent objective responses when treated with the combination of gemcitabine (Gemzar) and sunitinib (Sutent), according to the results of a small phase II study.

“Patients with rapidly progressive disease may have fundamentally differing disease pathogenesis and molecular studies are warranted to investigate disease drivers and potential therapeutic targets,” said Rana R. McKay, MD, of Dana-Farber Cancer Institute, who presented results of the study (Abstract 408) at the 2015 Genitourinary Cancers Symposium in Orlando, Fla.

The trial was a single-arm study conducted at three institutions. Enrolled patients had sarcomatoid (n=39) or poor-risk (n=33) renal cell carcinoma.  Patients were given sunitinib 37.5 mg orally for 2 weeks on and 1 week off, plus intravenous gemcitabine 1,000 mg/m² was given on day 1 and day 8 on a 21-day cycle. The researchers’ primary endpoint was objective response rate.

McKay and colleagues found an objective response rate of 26% for patients with sarcomatoid RCC and 24% for patients with poor-risk disease. Among patients with sarcomatoid disease, there was one patient with complete response and nine partial responses; in poor-risk disease, there were zero complete responses and eight partial responses.

The stable disease rate was 38% in patients with sarcomatoid disease and 39% in the patients with poor-risk. The researchers found that patients with tumors containing greater than 10% sarcomatoid histology were more likely to achieve stable disease or better when compared with patients with tumors with 10% or less sarcomatoid histology (100% stable disease or better vs 54.5%; P =.04).

Patients with sarcomatoid disease had a median time to progression of 5 months and a median overall survival of 10 months. Looking at patients with poor-risk disease, the median time to progression was 5.5 months, with a median overall survival of 15 months.

Grade 3 toxicity occurred in 49% of patients; the most common toxicities were neutropenia, anemia, fatigue, nausea, hypertension, thrombocytopenia, and hyponatremia. There were no treatment-related deaths.

“Tumors from 11 patients-eight sarcomatoid and three poor-risk-were subjected to genomic profiling using massively parallel sequencing technology or multiplex PCR and single-base extension reactions, and we identified no mutations in the potentially relevant genes which were analyzed or identified,” McKay said.