Survival analysis according to disease subtype in AVAGAST: First-line capecitabine and cisplatin plus bevacizumab (bev) or placebo in patients (pts) with advanced gastric cancer.

Abstract

5 Background: Gastric cancer (GC) is a heterogeneous disease that may be divided into distinct subtypes with different epidemiology, risk factors, and molecular expression profiles: proximal non-diffuse GC (type 1), diffuse GC (type 2), and distal non-diffuse GC (type 3). In clinical practice, GC subtypes are treated as a single disease. Regional efficacy differences were seen in AVAGAST: pts in Americas and Europe showed more evidence of benefit than Asia-Pacific pts. We analyzed outcomes in the phase III AVAGAST study according to GC subtype and region in order to test if GC subtype was prognostic of outcome and predictive of bev benefit. Methods: Pts were randomized and treated as previously described. The effect of treatment on overall survival (OS), measured by hazard ratio, was examined in an unplanned exploratory analysis using Cox proportional hazards models. Median OS was estimated using the Kaplan-Meier method. Results: 733 of 774 AVAGAST pts were included. Type 2 GC (52.1%) was more common than type 1 (9.5%) or type 3 (38.3%). Irrespective of treatment, pts with type 2 GC had worse outcome than type 3 GC (median OS 10.3 vs 11.7 mo; HR=0.82; 95% CI 0.68–1.00); non-Asian pts had the most dismal prognosis (8.0 vs 11.1 mo; HR=0.68; 95% CI 0.53–0.89). The table below describes the bev effect according to subtype. Non-Asian pts with GC type 2 and 3 appear to benefit from bev. Conclusions: In all regions, pts with type 3 GC had a better prognosis than type 2 GC. Bev therapy appeared to improve outcomes in non-Asian pts with type 2 and 3 GC. These data suggest that GC subtypes may be important predictors of pt outcome and warrant further prospective evaluation. [Table: see text]