Abstract
16042 Background: Expression of CAIX (a hypoxia induced protein and potential surrogate for VHL inactivation) and previously defined pathologic features (presence of alveolar features/absence of papillary/granular features) have been reported as independent predictors of outcome in pts with mRCC treated with immunotherapy. We attempted to validate the prognostic and predictive utility of CAIX expression and previously defined pathologic features in pts treated with VEGF-targeted therapy. Methods: We identified 112 pts with mRCC treated with VEGF-targeted therapy between 2001–2007. Paraffin-embedded tumor tissue was obtained on 86 pts: sunitinib (n=30), sorafenib (n=42), bevacizumab (n=12) or PTK787 (n=2) and immunostained with the M75 antibody against CAIX. CAIX expression levels and histologic findings were correlated with response rate (RR), tumor shrinkage (TS), treatment duration (TD) and overall survival (OS). Results: 64% of pts were male. 93% had prior nephrectomy. 71% had ≥2 metastatic sites and 44% had prior systemic, non-antiangiogenic therapies. 34% had poor-risk, 36% intermediate (int)-risk and 28% had good-risk Upton pathologic features. 66% of pts had high CAIX expression (> 85% tumor cells +). Median follow-up was 21 months. High CAIX expression correlated with higher RR, TS, TD and OS, although it did not reach statistical significance (TABLE). Similarly, pts with good Upton pathologic features had higher RR (p=0.24), TS (p=0.27) and TD (p=0.26). OS was significantly better in good-risk pts (p=0.02) compared to pts with int/poor-risk features. Conclusions: Although high CAIX expression is associated with a better outcome in pts with mRCC treated with VEGF-targeted agents, these trends did not meet statistical significance. Pts with good pathologic features had a higher OS than pts with poor/int features. Further analysis of these features will require additional samples and randomized studies. CAIX low (n=29) CAIX high (n=57) P-Value Response Rate (PR) 23% 35% p=0.75 (Fishers exact) Median TS -10% - 16% p=0.58 (Wilcoxon) Median TD 5.1 months 9.1 months p=0.12 (logrank) Median OS 20.5 months 33.2 months p=0.44 (logrank) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Antigenics, Aveo, Bayer/Onyx, Genentech, Novartis, Wyeth Pfizer Bayer/Onyx, Genentech, Novartis
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