scholarly journals A comparison between triplet and doublet chemotherapy in improving the survival of patients with advanced gastric cancer: a systematic review and meta-analysis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xinjian Guo ◽  
Fuxing Zhao ◽  
Xinfu Ma ◽  
Guoshuang Shen ◽  
Dengfeng Ren ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Advanced Gastric Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Triplet Chemotherapy ◽  
Asian Patients ◽  
Doublet Chemotherapy

Abstract Background Chemotherapy 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. Methods RCTs 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. Results Our 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. Conclusions Compared 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.

Third- and later-line treatment in advanced or metastatic gastric cancer: a systematic review and meta-analysis

2020 ◽  
Vol 16 (2) ◽  
pp. 4409-4418 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Angela Dalia Ricci ◽  
Ilaria Maggio ◽  
Maria Massucci ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Supportive Care ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Best Supportive Care ◽  
Free Survival

Aim: We performed a systematic review and meta-analysis to investigate the efficacy and safety of third-line (TLT) and salvage treatment (ST) in advanced or metastatic gastric cancer. Materials & methods: Eligible studies included randomized clinical trials assessing TLT and ST versus placebo or best supportive care. Outcomes of interest included: overall survival, objective response rate and disease control rate in TLT; progression-free survival in ST; grade 3–4 adverse events in ST. Results: The use of TLT and ST was superior to placebo or best supportive care in terms of prolonging overall survival and progression-free survival. Hematological toxicities were more frequent in ST. Conclusion: TLT and ST are considerable and tolerable treatment options for patients with advanced or metastatic gastric cancer. Given the substantial heterogeneities affecting the efficacy analyses, these results have to be interpreted cautiously.

A systematic review and meta-analysis of the randomized controlled trials on adjuvant intraperitoneal chemotherapy for advanced gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4614-4614 ◽  
Author(s):  
T. D. Yan ◽  
D. Black ◽  
P. H. Sugarbaker ◽  
Y. Yonemura ◽  
J. Zhu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Advanced Gastric Cancer ◽  
Intraperitoneal Chemotherapy ◽  
Data Extraction ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Abdominal Abscess ◽  
Term Survival

4614 Objectives: Despite the use of adjuvant systemic chemotherapy or radiotherapy, the long-term survival in patients with stage III and IV gastric cancer remains limited. The purpose of this systematic review and meta-analysis was to determine the effectiveness and safety of adjuvant intraperitoneal chemotherapy for patients with advanced gastric cancer. Methods: Studies eligible for this systematic review included those in which patients with gastric cancer were randomly assigned to receive surgery combined with intraperitoneal chemotherapy versus surgery without intraperitoneal chemotherapy. All forms of intraperitoneal chemotherapy in addition to surgery were included. There were no language restrictions. Quality of the trials was assessed by a predetermined checklist. The primary end-point of the meta-analysis was overall survival, defined as the time from random assignment to the last follow-up or death. Secondary end-points were the differences in the incidence of recurrence, morbidity and mortality. Results: Thirteen reports of randomised controlled trials (RCTs) were included for appraisal and data extraction. Ten reports were judged fair-quality and subjected to the meta-analysis. A significant improvement in survival was associated with hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) alone (HR = 0.60; 95% CI = 0.43 to 0.83; p = 0.002) or combined with early postoperative intraperitoneal chemotherapy (EPIC) (HR = 0.45; 95% CI = 0.29 to 0.68; p = 0.0002). Survival improvement was marginally significant (HR = 0.67; 95% CI = 0.44 to 1.01; p = 0.06) with normothermic intraoperative intraperitoneal chemotherapy, but not significant with EPIC alone or delayed postoperative intraperitoneal chemotherapy. Intraperitoneal chemotherapy was also found to be associated with higher risks for intra-abdominal abscess (RR = 2.37; 95% CI = 1.32 to 4.26; p = 0.003) and neutropenia (RR = 4.33; 95% CI = 1.49 to 12.61; p = 0.007). Conclusion: The present meta-analysis indicates that HIIC with or without EPIC after resection of advanced gastric primary cancer is associated with an improved overall survival. However, increased risks of intra-abdominal abscess and neutropenia are demonstrated. No significant financial relationships to disclose.

Pembrolizumab (pembro) versus standard of care chemotherapy (chemo) in patients with advanced gastric or gastroesophageal junction adenocarcinoma: Asian subgroup analysis of KEYNOTE-062.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4523-4523 ◽  
Author(s):  
Hironaga Satake ◽  
Keun Wook Lee ◽  
Hyun Cheol Chung ◽  
Jeeyun Lee ◽  
Kensei Yamaguchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Asian Population ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
End Points ◽  
Asian Patients

4523 Background: First-line treatment with pembro or pembro + chemo vs chemo alone was evaluated in patients with PD-L1 combined positive score (CPS) ≥1, HER2-negative advanced gastric cancer in the randomized, active-controlled, phase 3 KEYNOTE-062 study (NCT02494583). We present results from the Asian subpopulation receiving pembro monotherapy or chemo. Methods: Eligible patients were randomly assigned 1:1:1 to pembro 200 mg, pembro + chemo (cisplatin + 5-FU or capecitabine), or placebo + chemo every 3 weeks for ≤35 cycles (~2 years). Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary end points for this analysis were overall survival (OS) in patients with CPS ≥1 and patients with CPS ≥10; progression-free survival (PFS) and objective response rate (ORR) were exploratory end points. Data cutoff was March 26, 2019. Results: Globally, 256 patients received pembro monotherapy and 250 received chemo. Pembro was noninferior to chemo for OS in CPS ≥1 per prespecified margins (median OS, 10.6 vs 11.1 months, respectively; HR [99.2% CI], 0.91 [0.69-1.18]). In the Asian population 62 patients received pembro and 61 received chemo; 26 and 22 had CPS ≥10 (Table). Compared with the global population, Asian patients had a higher proportion of ECOG performance status 0, more diagnoses of stomach cancer, and a greater proportion with 0-2 metastatic sites. Median OS was longer with pembro than chemo using both CPS cutoffs (HR [95% CI]: CPS ≥1, 0.54 [0.35-0.82]; CPS ≥10, 0.43 [0.21-0.89]); 12- and 24-month OS rates were higher for pembro using both CPS cutoffs (12-month OS: CPS ≥1, 69% vs 54%; CPS ≥10, 81% vs 68%; 24-month OS: CPS ≥1, 45% vs 23%; CPS ≥10, 54% vs 27%). The HR (95% CI) for PFS was 1.11 (0.76-1.64) for CPS ≥1 and 0.71 (0.36-1.39) for CPS ≥10. Conclusions: In Asian patients with advanced gastric cancer, OS favored pembro in patients with CPS ≥1 and CPS ≥10. Clinical trial information: NCT02494583 . [Table: see text]

Matched therapies for advanced gastric cancer based on genotype: A real-world study in China.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16098-e16098
Author(s):  
Qin Liu ◽  
Ju Yang ◽  
Nandie Wu ◽  
Song Liu ◽  
Yipeng Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Control ◽  
Advanced Gastric Cancer ◽  
Real World ◽  
Systemic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Tumor Biopsy ◽  
Kit Mutation

e16098 Background: Systemic therapy options for patients with advanced gastric cancer (GC) are limited. We here presented the efficacy results for advanced GC patients matched to targeted therapies or immunotherapies based on the identification of tumor tissue genotypes. Methods: We selected 30 patients diagnosed between 2014 and 2020 with advanced GC at Nanjing Drum Tower Hospital, the affiliated Hospital of Nanjing University Medical School identified with actionable alterations and received ≥1 matched therapies. Tumor biopsy specimens from the patients were analyzed using NGS and/or selected immunohistochemistry and fluorescence in situ hybridization. Results: In these 30 patients, median age at diagnosis was 63 years (range 28-83) and 6 (20%) were female. In total, 11 (37%) harbored c-MET amplification/overexpression (received savolitinib or crizotinib, cohort A), 9 (30%) harbored HER2 mutation/overexpression (received RC48-ADC or trastuzumab, cohort B), 6 (20%) dMMR/MSI-H/TMB-H (received sintilimab, pembrolizumab, tislelizumab or nivolumab, combined with antivascular or not, cohort C), 2 (7%) KIT mutation/amplification (received imatinib or anlotinib, cohort D), 1 (3%) BRAF V600E mutation (received vemurafenib, cohort E) and 1 (3%) EGFR mutation (received afatinib, cohort F). Except for three patients in cohort C, all patients received at least one previous line systemic therapy. In cohort A, three of 11 patients had an objective response (1 complete response and 2 partial responses, objective response rate (ORR) 27%), disease control rate (DCR) was 45%, median progression-free survival (mPFS) was 2.1 months, and median overall survival (mOS) was 3.7 months. In cohort B, ORR was 44% (4/9), DCR was 78% (7/9), mPFS and mOS was 3.1 months and 5.5 months, respectively. In cohort C, ORR was 17% (1/6), DCR was 67% (4/6), mPFS and mOS was 1.9 months and 6.8 months, respectively. In cohort D, no patient had objective response or disease control. In cohort E, the one patient had PR. Stable disease was observed in the patient in cohort F. In all cohorts, ORR was 30% (9/30), DCR was 60% (18/30), mPFS and mOS was 2.7 months and 5.8 months, respectively. Conclusions: Overall, 30 patients with advanced GC were treated with matched therapies according to specific genotype. These real-world outcomes suggested that matched therapies for advanced GC has promising efficacy, supporting the adoption of genotyping in treatment determination.

scholarly journals Pharmacogenetic Association between XRCC1 Polymorphisms and Response to Platinum-Based Chemotherapy in Asian Patients with NSCLC: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Ningning Zhang ◽  
Yushu Ouyang ◽  
Jianlan Chang ◽  
Ping Liu ◽  
Xiangyang Tian ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Gene Dosage ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Gene Dosage Effect ◽  
Asian Patients ◽  
Hazard Ratios ◽  
Platinum Based Chemotherapy ◽  
Study Heterogeneity

Background. Platinum-based chemotherapy plays an antitumor role by damaging DNA. X-ray repair crosscomplementing protein 1 (XRCC1) participates in DNA repair and thus affects the sensitivity to platinum drugs. Two polymorphisms of XRCC1, rs25487 (Arg399Gln) and rs1799782 (Arg194Trp), have been widely studied for the association with clinical outcomes of platinum-based chemotherapy in Asian patients with non-small-cell lung cancer (NSCLC), but the results remain inconclusive. Thus, we performed the present meta-analysis. Methods. Literature search was performed in PubMed, Web of Science, and EMBASE up to June 2019. Odds ratios (ORs) for objective response ratio (ORR), Cox proportional hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS), and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the association strengths between XRCC1 polymorphisms and clinical outcomes. Comparisons were performed in homozygous, heterozygous, dominant, and recessive models. Results. Finally, a total of 23 studies involving 5567 patients were included in the meta-analysis. Compared to ArgArg of rs25487, GlnGln ( OR = 1.71 , 95% CI: 1.16-2.52, p = .007 , I 2 = 56.8 % ) and GlnArg ( OR = 1.23 , 95% CI: 1.07-1.40, p = .003 , I 2 = 29.0 % ) were associated with higher ORR. Meanwhile, GlnGln indicated a favorable OS ( HR = 0.60 , 95% CI: 0.40-0.88) and PFS ( HR = 0.64 , 95% CI: 0.46-0.90). We also found positive associations between rs1799782 and ORR in all comparison models with low between-study heterogeneity. The association strength increased with the number of variant alleles (TrpTrp vs. ArgArg: OR = 1.73 , 95% CI:1.31-2.27; TrpArg vs. ArgArg: OR = 1.28 , 95% CI: 1.06-1.55), suggesting a gene dosage effect. In addition, TrpTrp predicted a longer OS. Conclusion. Our results showed that rs25487 and rs1799782 of XRCC1 are potential markers to predict clinical outcomes of platinum-based chemotherapy in Asian patients with NSCLC.

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