Dataset Information

Anti-EGFR Monoclonal Antibodies in Advanced Biliary Tract Cancer: A Systematic Review and Meta-analysis.

ABSTRACT: BACKGROUND:Despite several clinical trials and advances in understanding the genetic basis of biliary tract cancer (BTC), the addition of epidermal growth factor receptor (EGFR) targeted therapy does not seem to enhance the activity of first-line chemotherapy (CHT). MATERIALS AND METHODS:We carried out a meta-analysis of available randomized clinical trials to assess the efficacy and safety of gemcitabine-based first-line CHT plus monoclonal antibodies against EGFR (EGFR-mAbs) in advanced or metastatic BTC. RESULTS:In the overall population, the pooled hazard ratio for overall (OS) and progression-free (PFS) survival were 0.82 (95% confidence interval=0.64-1.06) and 0.88 (95% confidence intervaI=0.73-1.08), respectively. No differences were detected in objective response rate between the two groups. Patients treated with gemcitabine-based CHT plus EGFR-mAbs showed a statistically significant increased risk of grade 3-4 neutropenia, grade 3-4 thrombocytopenia and especially grade 3-4 skin rash. CONCLUSION:The addition of EGFR-mAbs to gemcitabine-based first-line CHT does not significantly improve overall and progression-free survival, nor the objective response rate in patients with advanced BTC and increases the risk of hematological and cutaneous adverse drug events.

SUBMITTER: Rizzo A

PROVIDER: S-EPMC7157865 | biostudies-literature | 2020 Mar-Apr

REPOSITORIES: biostudies-literature

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Anti-EGFR Monoclonal Antibodies in Advanced Biliary Tract Cancer: A Systematic Review and Meta-analysis.

Rizzo Alessandro A Frega Giorgio G Ricci Angela Dalia AD Palloni Andrea A Abbati Francesca F DE Lorenzo Stefania S Deserti Marzia M Tavolari Simona S Brandi Giovanni G

In vivo (Athens, Greece) 20200301 2

<h4>Background</h4>Despite several clinical trials and advances in understanding the genetic basis of biliary tract cancer (BTC), the addition of epidermal growth factor receptor (EGFR) targeted therapy does not seem to enhance the activity of first-line chemotherapy (CHT).<h4>Materials and methods</h4>We carried out a meta-analysis of available randomized clinical trials to assess the efficacy and safety of gemcitabine-based first-line CHT plus monoclonal antibodies against EGFR (EGFR-mAbs) in ...[more]

PMID: 32111744

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Project description:BackgroundTargeted therapy (TT) has resulted in controversial efficacy as first-line treatment for biliary tract cancer (BTC). More efficacy comparisons are required to clarify the overall effects of chemotherapy (CT) combined with TT and CT alone on advanced BTC.AimTo conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.MethodsThe PubMed, EMBASE, ClinicalTrials, Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022. Only randomized clinical trials (RCTs) including comparisons between the combination of gemcitabine-based CT with TT and CT alone as first-line treatment for advanced BTC were eligible (PROSPERO-CRD42022313001). The odds ratios (ORs) for the objective response rate (ORR) and hazard ratios (HRs) for both progression-free survival (PFS) and overall survival (OS) were calculated and analyzed. Subgroup analyses based on different targeted agents, CT regimens and tumor locations were prespecified.ResultsNine RCTs with a total of 1361 individuals were included and analyzed. The overall analysis showed a significant improvement in ORR in patients treated with CT + TT compared to those treated with CT alone (OR = 1.43, 95%CI: 1.11-1.86, P = 0.007) but no difference in PFS or OS. Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor (OR = 1.67, 95%CI: 1.17-2.37, P = 0.004) but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor. Notably, patients who received a CT regimen of gemcitabine + oxaliplatin in the CT + TT arm had both a higher ORR (OR = 1.75, 95%CI: 1.20-2.56, P = 0.004) and longer PFS (HR = 0.83, 95%CI: 0.70-0.99, P = 0.03) than those in the CT-only arm. Moreover, patients with cholangiocarcinoma treated with CT + TT had significantly increased ORR and PFS (ORR, OR = 2.06, 95%CI: 1.27-3.35, PFS, HR = 0.79, 95%CI: 0.66-0.94).ConclusionCT + TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes, and highlighting the importance of CT regimens and tumor types in the application of TT.

Project description:BACKGROUND: BRAF mutation has been investigated as a prognostic factor in metastatic colorectal cancer (mCRC) undergoing anti-EGFR monoclonal antibodies (moAbs), but current results are still inconclusive. The aim of this meta-analysis was to evaluate the relationship between BRAF mutation status and the prognosis of mCRC patients treated with moAbs. METHODS: Eligible studies were identified by systematically searching Pubmed, the Cochrane Library, Web of Knowledge, and OVID. Risk ratio (RR) for overall response rate (ORR), Hazard ratios (HRs) for Progression free survival (PFS) and Overall survival (OS) were extracted or calculated. Prespecified subgroup analyses were conducted in KRAS wild-type and in different study types. The source of between-trial variation was explored by sensitivity analyses. Quality assessment was conducted by the Hayden's criteria. RESULTS: A total of twenty one trials including 5229 patients were identified for the meta-analysis. 343 patients displayed BRAF mutations of 4616 (7.4%) patients with known BRAF status. Patients with BRAF wild-type (WT) showed decreased risks of progression and death with an improved PFS(HR 0.38, 95% confidence intervals 0.29-0.51) and an improved OS (HR 0.35 [0.29-0.42]), compared to BRAF mutant. In KRAS WT population, there were even larger PFS benefit (HR 0.29[0.19,0.43]) and larger OS benefit (HR 0.26 [0.20,0.35]) in BRAF WT. A response benefit for BRAF WT was observed (RR 0.31[0.18,0.53]) in KRAS WT patients, but not observed in unselected patients (RR 0.76 [0.43-1.33]). The results were consistent in the subgroup analysis of different study types. Heterogeneity between trials decreased in the subgroup and explained by sensitivity analysis. No publication bias of ORR, PFS and OS were detected. CONCLUSIONS: The results indicate that BRAF mutant is a predictive biomarker for poor prognosis in mCRC patients undergoing anti-EGFR MoAbs therapy, especially in KRAS WT patients. Additional large prospective trials are required to confirm the predictive role of BRAF status.

Project description:BackgroundThe use of standard cytotoxic chemotherapy seems to have reached a "treatment plateau". The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC.MethodsAccording to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted.ResultsThe research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001).ConclusionAdding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone.

Dataset Information

Anti-EGFR Monoclonal Antibodies in Advanced Biliary Tract Cancer: A Systematic Review and Meta-analysis.

Publications

Anti-EGFR Monoclonal Antibodies in Advanced Biliary Tract Cancer: A Systematic Review and Meta-analysis.

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