Metastatic renal cell carcinoma (mRCC) patients (pts) with sarcomatoid features treated with VEGF-targeted therapy

Abstract

5102 Background: Sarcomatoid differentiation is an aggressive RCC variant associated with poor outcomes. There is limited data regarding the use of VEGF-targeted therapy in these pts. Methods: Pts with mRCC with sarcomatoid features treated with VEGF- targeted therapy were identified. Tissue nephrectomy samples were reviewed by a single pathologist and the percentage of sarcomatoid elements were estimated. Objective response, tumor burden shrinkage, progression-free (PFS) and overall survival (OS) were determined. A comparison group of 29 pts with clear cell RCC without sarcomatoid components (NS) also treated with anti-VEGF therapy and matched for gender, risk factors and treatment received were also evaluated. Results: Sarcomatoid differentiation was found in 43 pts: 33 clear cell, 1 papillary, 1 chromophobe, 1 mixed and 7 unclassified RCC subtypes. The median percentage of sarcomatoid elements was 20% (range, 5–80%). Pts received sunitinib (49%), sorafenib (28%), bevacizumab (19%) or sunitinib + bevacizumab (5%). All pts had prior nephrectomy and 44% had 1 prior systemic therapy. Tumor shrinkage was documented in 47% of pts, and median shrinkage was 2% (range, -85% to +127%). Eight pts (19%) achieved partial responses (PR), 21 (49%) stable disease (SD) and 14 pts (33%) had progressive disease (PD) as their best response. Median PFS and OS were 5.3 months and 11.8 months respectively. The NS group had greater tumor shrinkage (29% vs. 5%, p=0.01) and median PFS (13.2 vs. 5.5 months, p=0.05) than the sarcomatoid group. There was no significant difference in median PFS based upon treatment given. Pts with <20% sarcomatoid elements appeared to have better responses to VEGF-targeted therapy (Table). Conclusions: Pts with mRCC with sarcomatoid differentiation demonstrate objective responses and tumor shrinkage with anti-VEGF therapy, particularly with <20% sarcomatoid elements. Clinical Outcome Based on Percentage of Sarcomatoid Components Sarcomatoid Percentage PR SD PD Tumor Shrinkage (median, range) Median PFS (months) Median OS (months) < 20% 33% 40% 17% -6.5% (-58.0, 53.0) 7.9 16.4 ≥20% 0 30% 69% +23.0% (-19.1, 47.0) 3.1 6.4 p-value 0.006 0.05 0.49 0.16 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Antigenics, Bayer, Genentech™ BioOncology, Novartis, Onyx, Pfizer Oncology, Wyeth Bayer, Genentech™ BioOncology, Novartis, Onyx, Pfizer Oncology, Wyeth Bayer, Genentech™ BioOncology, Pfizer Oncology, Wyeth