Abstract
BackgroundStudies of anti-angiogenic agents (AAs), combined with chemotherapy (chemo) or as monotherapy in metastatic oesophago-gastric cancer (mOGC), have reported mixed outcomes. We undertook systematic review and meta-analysis to determine their overall benefits and harms.MethodsRandomized controlled trials in mOGC were sought investigating the addition of AAs to standard therapy (best supportive care or chemo). The primary endpoint was overall survival (OS) with secondary endpoints progression-free survival (PFS), overall response rate (ORR) and toxicity. Estimates of treatment effect from individual trials were combined using standard techniques. Subgroup analyses were performed by line of therapy, region, age, performance status, histological type, number of metastatic sites, primary site, mechanism of action and HER2 status.ResultsFifteen trials evaluating 3502 patients were included in quantitative analysis. The addition of AAs was associated with improved OS: HR 0·81 (95% CI 0·75–0·88, p<0·00001) and improved PFS: HR 0·68 (95% CI 0·63–0·74, p<0·00001). Subgroup analyses favoured greater benefit for OS in 2nd/3rd line settings (HR 0·74) compared to 1st-line settings (HR 0·91) (X2 = 6·00, p = 0·01). OS benefit was seen across all regions—Asia (HR 0·83) and rest of world (HR 0·75)—without significant subgroup interaction. Results from 8 trials evaluating 2602 patients were pooled for toxicity > = Grade 3: with OR 1·39 (95% CI 1·17–1·65).ConclusionsThe addition of AAs to standard therapy in mOGC improves OS. Improved efficacy was only observed in 2nd- or 3rd-line setting and not in 1st-line setting. Consistent OS benefit was present across all geographical regions. This benefit is at the expense of increased overall toxicity.
Highlights
Gastric cancer is the fifth most common malignancy diagnosed worldwide and the 3rd leading cause of cancer mortality[1]
The addition of angiogenic agents (AAs) was associated with improved overall survival (OS): hazard ratio (HR) 0Á81 and improved progression-free survival (PFS): HR 0Á68
We undertook this systematic review and meta-analysis to evaluate the overall effect of antiangiogenic agents, in combination with chemotherapy and as monotherapy, in the treatment of metastatic oesophago-gastric cancer, with respect to the outcomes of overall survival, progression-free survival, response rate, toxicity measures and quality of life
Summary
Gastric cancer is the fifth most common malignancy diagnosed worldwide and the 3rd leading cause of cancer mortality[1]. Median survival of patients with metastatic oesophago-gastric cancer (mOGC) is less than 12 months with currently available treatment[2]. The survival of patients with HER-2 positive mOGC is better with a median survival of 16 months[3]. Antiangiogenic agents (AAs), both antibodies and tyrosine kinase inhibitors (TKIs), targeting angiogenic signalling pathways such as VEGF or its receptors, have been tested in the treatment of mOGC. We undertook this systematic review and meta-analysis to evaluate the overall effect of antiangiogenic agents, in combination with chemotherapy and as monotherapy, in the treatment of metastatic oesophago-gastric cancer (mOGC), with respect to the outcomes of overall survival, progression-free survival, response rate, toxicity measures and quality of life. Studies of anti-angiogenic agents (AAs), combined with chemotherapy (chemo) or as monotherapy in metastatic oesophago-gastric cancer (mOGC), have reported mixed outcomes. We undertook systematic review and meta-analysis to determine their overall benefits and harms
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