Abstract
BackgroundChemotherapy can improve the survival of patients with advanced gastric cancer. However, whether triplet chemotherapy can further improve the survival of patients with advanced gastric cancer compared with doublet chemotherapy remains controversial. This study reviewed and updated all published and eligible randomized controlled trials (RCTs) to compare the efficacy, prognosis, and toxicity of triplet chemotherapy with doublet chemotherapy in patients with advanced gastric cancer.MethodsRCTs on first-line chemotherapy in advanced gastric cancer on PubMed, Embase, and the Cochrane Register of Controlled Trials and all abstracts from the annual meetings of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology conferences up to October 2018 were searched. The primary outcome was overall survival, while the secondary outcomes were progression-free survival (PFS), time to progress (TTP), objective response rate (ORR), and toxicity.ResultsOur analysis included 23 RCTs involving 4540 patients and 8 types of triplet and doublet chemotherapy regimens, and systematic review and meta-analysis revealed that triplet chemotherapy was superior compared with doublet chemotherapy in terms of improving median OS (HR = 0.92; 95% CI, 0.86–0.98; P = 0.02) and PFS (HR = 0.82; 95% CI, 0.69–0.97; P = 0.02) and TTP (HR = 0.92; 95% CI, 0.86–0.98; P = 0.02) and ORR (OR = 1.21; 95% CI, 1.12–1.31; P < 0.0001) among overall populations. Compared with doublet chemotherapy, subgroup analysis indicated that OS improved with fluoropyrimidine-based (HR = 0.80; 95% CI, 0.66–0.96; P = 0.02), platinum-based (HR = 0.75; 95% CI, 0.57–0.99; P = 0.04), and other drug-based triplet (HR = 0.79; 95% CI, 0.69–0.90; P = 0.0006) chemotherapies while not with anthracycline-based (HR = 0.70; 95% CI, 0.42–1.15; P = 0.16), mitomycin-based (HR = 0.81; 95% CI, 0.47–1.39; P = 0.44), taxane-based (HR = 0.91; 95% CI, 0.81–1.01; P = 0.07), and irinotecan-based triplet (HR = 1.01; 95% CI, 0.82–1.24; P = 0.94) chemotherapies. For different patients, compared with doublet chemotherapy, triplet chemotherapy improved OS (HR = 0.89; 95% CI, 0.81–0.99; P = 0.03) among Western patients but did not improve (HR = 0.96; 95% CI, 0.86–1.07; P = 0.47) that among Asian patients.ConclusionsCompared with doublet chemotherapy, triplet chemotherapy improved OS, PFS, TTP, and ORR in patients with advanced gastric cancer in the population overall, and improved OS in Western but not in Asian patients.
Highlights
Chemotherapy can improve the survival of patients with advanced gastric cancer
Our analysis included 23 randomized controlled trials (RCTs) involving 4540 patients and 8 types of triplet and doublet chemotherapy regimens, and systematic review and meta-analysis revealed that triplet chemotherapy was superior compared with doublet chemotherapy in terms of improving median overall survival (OS) (HR = 0.92; 95% confidence intervals (95% CIs), 0.86–0.98; P = 0.02) and progression-free survival (PFS) (HR = 0.82; 95% CI, 0.69–0.97; P = 0.02) and time to progress (TTP) (HR = 0.92; 95% CI, 0.86–0.98; P = 0.02) and objective response rate (ORR) (OR = 1.21; 95% CI, 1.12–1.31; P < 0.0001) among overall populations
Subgroup analysis indicated that OS improved with fluoropyrimidine-based (HR = 0.80; 95% CI, 0.66–0.96; P = 0.02), platinum-based (HR = 0.75; 95% CI, 0.57–0.99; P = 0.04), and other drug-based triplet (HR = 0.79; 95% CI, 0.69–0.90; P = 0.0006) chemotherapies while not with anthracycline-based (HR = 0.70; 95% CI, 0.42–1.15; P = 0.16), mitomycin-based (HR = 0.81; 95% CI, 0.47–1.39; P = 0.44), taxane-based (HR = 0.91; 95% CI, 0.81–1.01; P = 0.07), and irinotecan-based triplet (HR = 1.01; 95% CI, 0.82–1.24; P = 0.94) chemotherapies
Summary
Chemotherapy can improve the survival of patients with advanced gastric cancer. Whether triplet chemotherapy can further improve the survival of patients with advanced gastric cancer compared with doublet chemotherapy remains controversial. 80–90% of patients with gastric cancer are diagnosed at an advanced stage, implying that the tumor either cannot be resected through operation or developed a recurrence or metastasis after surgery [2, 3]. The prognosis of these patients remains very poor, and the median survival time is only about 12 months [3]. For first-line setting, only trastuzumab or ramucirumab combined with chemotherapy is approved, with only about 10% of patients experiencing HER2 overexpression [7]
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