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

Abstract

e15076 Background: Sunitinib is a standard front-line treatment for metastatic renal cell carcinoma (mRCC) patients (pts), but is not proven to be beneficial in pts with poor-risk clinical features or sarcomatoid histology. These two populations of mRCC pts typically have short median survival. We are conducting a phase 2 study of combination treatment with sunitinib and gemcitabine in clinical or pathologic poor-risk mRCC. Methods: Eligible pts with mRCC have either elements of sarcomatoid histology or poor-risk disease by modified clinical criteria (3 or more of the following: ECOG PS > 1, time from diagnosis to treatment < 12 months, anemia, hypercalcemia, LDH ≥ 1.5 normal, or ≥ 2 sites of disease). Treatment consists of 21-day cycles of sunitinib 37.5 mg daily (2 weeks on, 1 week off), and gemcitabine 1000 mg/m2 on days 1 and 8. Pts may have received no more than one prior therapy for mRCC. A total of 36 pts will be enrolled, and the primary endpoint is radiographic response rate by RECIST. Secondary endpoints include progression free survival (PFS), safety and tolerability, and overall survival. Results: Twenty five pts have been treated to date. Of these, 13 were eligible due to sarcomatoid histology, and the remaining pts were eligible based on clinical poor-risk criteria. Among 20 patients evaluable for response, 5 had confirmed partial response (25%), including 3 with sarcomatoid histology, and an additional 10/20 exhibited stable disease for ≥ 12 weeks (50%). None of 5 pts with underlying papillary or chromophobe RCC histology has responded. Median PFS is 4.6 months among the patients with sarcomatoid RCC (range 2-12 months), 5.9 months among clinical poor- risk pts (range: 1-8 months), and 4.8 months overall. Five pts have been removed from study due to adverse events, including fatigue, hemolytic anemia, renal dysfunction, and cumulative grade 2 toxicities. Median overall survival has not been reached. Conclusions: Treatment of mRCC pts with sarcomatoid histology or clinical poor-risk features using a combination regimen of sunitinib and gemcitabine results in a clinical benefit rate of 75% and PFS of 4.8 months. Further prospective study of this regimen is warranted in these subpopulations of mRCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories, Aggenix, Antigenics, AVEO, Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx, Pfizer, Roche, Wyeth Pfizer, Wyeth Amgen, Bayer, Genentech, Novartis, Pfizer