First-line systemic therapy for advanced gastric cancer: a systematic review and network meta-analysis

Abstract

Background: Systemic therapy is the standard treatment against advanced gastric cancer. Fluoropyrimidine plus platinum doublet has been recommended as the preferred first-line strategy. However, there is still a lack of a comprehensive and hierarchical evidence that compares all eligible literature simultaneously. Methods: Record retrieval was conducted in PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, ASCO, and ESMO meeting library from inception to October 2018. Randomized controlled trials featuring comparisons between different first-line systemic treatments against advanced gastric cancer were eligible. Overall survival was utilized as the primary endpoint. Pairwise and network calculations were based on a random-effects model and the hierarchical ranking was numerically indicated by P-score. All procedures were conducted according to Cochrane Handbook 5.1 and PRISMA for Network Meta-analysis (Registration identifier: CRD42018084951). Results: A total of 119 studies were eligible for our pooled analysis. Concerning general analysis, ‘fluoropyrimidine plus platinum-based triplet’ topped the overall survival hierarchy (HR 0.91 [0.83–0.99], P-score = 0.903, p = 0.04) while it ranked in second place for progression-free survival and objective response rate. However, it displayed worse tolerability against ‘fluoropyrimidine plus platinum doublet’. More specifically, ‘Capecitabine plus cisplatin-based triplet plus targeted medication’ topped the ranking among all fluoropyrimidine plus platinum-based regimens in additional analysis. Nevertheless, it did not reach statistical advantage against fluoropyrimidine plus oxaliplatin doublet in terms of survival benefits, while still displaying significantly worse safety profile. Conclusions: Taken together, fluoropyrimidine plus oxaliplatin doublet (especially capecitabine or S-1) should still be considered as the preferred first-line regimen owing to its comparable survival benefits and lower toxicity.

Efficacy and Safety of Astragalus-Containing Traditional Chinese Medicine Combined With Platinum-Based Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis

“…In China, patients with AGC have poor clinical outcomes and a low 5-year survival rate of <20% ( 53 ). PBC is widely used and plays a crucial role in the treatment of AGC ( 54 ). However, the survival benefit in patients with AGC is still limited; therefore, it is necessary to develop effective combination therapies to increase the efficacy of PBC and reduce side effects in order to prolong the survival time and improve QOL in these patients.…”

PITPNA-AS1 Activated by H3K27ac&nbsp;Sponged miR-98-5p&nbsp;to Regulate Cisplatin Resistance in Gastric Cancer

“…For locally advanced disease, adjuvant or neoadjuvant therapy which recognized as the optimal therapeutic option is usually introduced with surgery owing to its curability 30 . Fluoropyrimidine plus oxaliplatin doublet is considered as the preferred rst-line regimen due to its comparable survival bene ts and lower toxicity 32 . Overcoming resistance is still a challenge in GC chemotherapy.…”

CircRNA DONSON contributes to cisplatin resistance in gastric cancer cells by regulating miR-802/BMI1 axis

“…Drug resistance has been recognized as one of the difficulties for clinical tumor chemotherapy. DDP is often adopted as a first-line drug for the chemotherapy of gastric cancer patients [12], which can suppress cell vitality and kill tumor cells primarily through inducing apoptosis [13]. However, studies have shown the occurrence of DDP resistance in patients with gastric cancer, which leads to chemotherapy failure and poor prognosis [14].…”