Antiangiogenic therapy (AT) has demonstrated a significant improvement in overall survival (OS) in advanced gastro-esophageal cancer (AGC) in the second line (2L) setting. However results in the first line (1L) are unalike and its role is still unclear. The small size of the majority of the studies may be underestimating the effect of this treatment. We aimed to perform a systematic review and meta-analysis of randomized clinical trials (RCT) in this setting to synthesize the available data and help decision-making.
A systematic search was performed through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and ASCO meeting abstracts up to April 2016 to identify RCTs for AGC comparing standard treatment + AT vs standard treatment alone in 1L and 2L. Studies were reviewed by two authors and discrepancies were resolved by consensus or by a third author. Data including progression-free survival (PFS), OS and response rate (RR) were extracted. The primary endpoint was OS. A meta-analysis (MA) with fixed and random effects models comparing the different regimens with direct comparisons was conducted.
Ten RCT including 2769 patients were identified. Six evaluated AT in 1L, and four in 2L. Overall, the pooled analysis demonstrated that AT improved OS (HR = 0.84, 95% CI 0.77-0.92) and PFS (HR = 0.74, 95% CI 0.61-0.89). When 1L and 2L RCT were analyzed separately, a statistically significantly improvement in OS (HR = 0.79, 95%CI 0.70-0.89,p = 0.0001) and PFS (HR= 0.56, 95% CI 0.45-0.70,p
The results of direct MA suggest that AT vs. non-AT improves OS and PFS for patients in the 2L setting for AGC, however no benefit was demonstrated in the 1L.
Clinical trial identification
Legal entity responsible for the study
Hospital Universitario 12 de Octubre
All authors have declared no conflicts of interest.