A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?

Abstract

It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005-2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655-0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%CI 0.847-1.370; p D 0.543). Meta-analysis of HER-2 pathway confirmed improvement in terms of survival outcome, already known for this class of drugs (HR 0.823; p D 0.004). Pooled analysis demonstrated a significant survival benefit (OS: HR 0.823; PFS: HR 0.762) with acceptable tolerability profile for targeted-based therapies as compared to conventional treatments. This finding conflicts with the outcome of most individual studies, probably due to poor trial design or patients selection. In conclusion, our findings demonstrate a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents.

Management of advanced gastric cancer: An overview of major findings from meta-analysis

“…The efficacy of targeted therapy was evaluated in three meta-analyses [10, 18, 22]. As for OS, one of them favored targeted therapy of antiangiogenic and HER2 pathway but not for EGFR pathway compared with conventional chemotherapy [10].…”

“…As for OS, one of them favored targeted therapy of antiangiogenic and HER2 pathway but not for EGFR pathway compared with conventional chemotherapy [10]. One showed that in patients with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0, targeted therapy did not report a significant benefit over BSC.…”

“…Another meta-analysis that compared anti-VEGF therapy with non-anti-VEGF therapy favored anti-VEGF therapy regarding OS [22]. When it comes to RR, one of them favored anti-HER2 agents but not for anti-EGFR and anti-angiogenic agents [10]. One comparing anti-VEGF therapy with non-anti-VEGF therapy favored anti-VEGF therapy in terms of objective RR [22].…”

“…One meta-analysis did not reported relevant data. Only one meta-analysis evaluated PFS, which indicated that the targeted therapy of anti-angiogenic and HER2 pathway but not EGFR pathway was superior to conventional chemotherapy [10]. Also, only one meta-analysis reported recurrence-free survival (RFS) that anti-VEGF agents reported a significant benefit over non-anti-VEFG agents [22].…”

“…Also, only one meta-analysis reported recurrence-free survival (RFS) that anti-VEGF agents reported a significant benefit over non-anti-VEFG agents [22]. As for toxicity, one meta-analysis showed that the incidence of diarrhea and rash was higher in targeted therapy [10]; another found that grade 3 or 4 thrombocytopenia, diarrhea, and hypertension was significantly higher in anti-VEGF therapy compared to non-anti-VEFG therapy [22]. …”