Efficacy  and toxicities of adding molecular targeted agents to first-line chemotherapy in the treatment of advanced biliary tract cancer: a systematic review and meta-analysis

Zhao, Sheng; Miao, Yanping; Wang, Ruijun; Guo, Haidong; Jin, Feng; Guo, Xiuling; Luo, Tianyou

doi:10.2147/ott.s110926

Cited by 4 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There has been an interest in identification of potential targets in combination with a precision medicine approach for patients with BTC [ 5 ]. Unfortunately, none of the studies completed to date have improved the current standard of care [ 6 , 7 ]. Results from studies targeting Fibroblast Growth Factor Receptor (FGFR) [ 8 , 9 , 10 ] and isocitrate dehydrogenase (IDH) [ 11 ] (predominantly in intra-hepatic cholangiocarcinoma (ICC)) show promise and are expected to change the treatment paradigm for patients with ICC, although final results of ongoing studies are awaited for confirmation of real benefit (e.g.…”

Section: Introductionmentioning

confidence: 99%

The HER3 pathway as a potential target for inhibition in patients with biliary tract cancers

et al. 2018

View full text Add to dashboard Cite

IntroductionExpression of human epidermal growth factor receptor (HER)2 and HER3 have been investigated in small BTC studies using variable scoring systems.MethodsHER2 and HER3 overexpression/amplification were explored following internationally agreed guidelines using immunohistochemistry (IHC) and fluorescent in-situ hybridisation (FISH), respectively. Logistic regression and survival analysis (Kaplan Meier, Log rank test and Cox Regression) were used for statistical analysis.ResultsSixty-seven eligible patients with Stage I/II (31.3%) or III/IV (68.7%) disease at diagnosis were included. Membrane HER2 overexpression/amplification was identified in 1 patient (1%). HER3 overexpression was predominantly cytoplasmic; the rate of overexpression/amplification of HER3 in membrane and cytoplasm was 16% [ampullary cancer (AMP) (1/13; 8%), gallbladder cancer (GBC) (1/10; 10%), intra-hepatic cholangiocarcinoma (ICC) (6/26; 23%), extra-hepatic cholangiocarcinoma (ECC) (3/18; 17%)] and 24% [AMP (1/13; 8%), GBC (1/10; 10%), ICC (10/26; 38%), ECC (4/18; 22%)], respectively.ConclusionsA significant subset of patients with BTC expressed HER3. Inhibition of HER3 warrants further investigation. A better understanding of the downstream effects of HER3 in BTC requires further mechanistic investigations to identify new biomarkers and improve patient selection for future clinical trials.

show abstract

Section: Introductionmentioning

confidence: 99%

The HER3 pathway as a potential target for inhibition in patients with biliary tract cancers

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In terms of safety, toxicity has been reported including: neutropenia, thrombocytopenia, skin rash, nausea, vomiting, diarrhea, fatigue, anemia, peripheral neuropathy, AST/ALT elevation, etc. Among them, only neutropenia [14] (RR=1.95,95%CI 1.13-1.36), rash [14] (RR=18.11, 95%CI 5.13-63.91) and diarrhea [23] (RR=2.48,95%CI 1.2-5.10) were higher in the experimental group than in the control group. However, the risk of neutropenia and diarrhea has been inconsistent in different meta-analyses, For example, neutropenia reported by Xin ZHUANG [13] (RR=1.37,95%CI 0.89-2.21) and diarrhea reported by ALESSANDRO RIZZO [14] (RR=1.65,95%CI 0.89-3.04) showed no difference in risk between the two groups.…”

Section: Gemcitabine-based Chemotherapymentioning

confidence: 89%

“…Four studies investigated the efficacy and safety of gemcitabine-based chemotherapy + targeted therapy versus gemcitabine-based chemotherapy alone [13,14,22,23] (Table 2). Targeted therapies are typically epidermal growth factor receptor or vascular endothelial growth factor receptor inhibitors (anti-EGFR/VEGFR).…”

Section: Gemcitabine-based Chemotherapymentioning

confidence: 99%

Chemotherapy and targeted therapy for advanced biliary tract cancers：An umbrella review

Wang

Wen

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Malignant tumors of the biliary system have high malignancy and strong invasiveness, and are usually found in late stages with poor prognosis. For patients with advanced biliary tract cancer, chemotherapy and targeted therapy are one of the options to improve prognosis and delay tumor progression. The purpose of this study was to comprehensively evaluate the safety and efficacy of various chemotherapy regimenfor advanced biliary carcinoma. Methods : An umbrella review method was adopted, which aims to summarize the evidence from multiple studies around a research topic. Evidence from meta analyses up to 09 April 2022 were identified using PubMed, Web of Science, the Cochrane database, as well as manual screening. Eligible studies were screened according to inclusion and exclusion criteria. This study had been registered at PROSPERO (CRD42022324548).For each eligible study, we extracted the data of general characteristics and the main findings. The methodological quality of the included studies were assessed by AMSTAR2 and the quality of evidence was evaluated by the GRADE. Results : A total of 1833 articles were searched, 14 unique articles with 94 outcomes were identified by eligibility criteria. The incidence of skin rash (RR=18.11,95%CI 5.13-63.91) and diarrhea (RR=2.48,95%CI 1.2-5.10) was higher in patients receiving gemcitabine-based chemotherapy plus targeted therapy than in patients receiving gemcitabine alone. Patients receiving gemcitabine-containing chemotherapy developed leukopenia (OR=7.17, 95%CI 1.43-36.08), anemia (OR=7.04, 95%CI 2.59-19.12), thrombocytopenia (RR=2.45, 95%CI 1.39-4.32) and neutropenia (RR=3.30, 95%CI 1.04-10.50) were significantly higher than gemcitabine-free regimens. In addition, patients receiving S-1 monotherapy had significantly better ORR (RR=2.46,95%CI 1.27-4.57) than patients receiving S-1+gemcitabine. Patients receiving fluoropyrimidine-based chemotherapy had longer OS (HR=0.83, 95%CI 0.7-0.99), higher DCR (0R=5.18, 95%CI 3.3-10.23), and higher ORR (0R=3.24, 95%CI 1.18-8.92) compared with 5-FU/LV monotherapy or supportive therapy. Surprisingly, there was also evidence that gemcitabine-based chemotherapy did not improve postoperative patients' OS (HR=0.91, 95%CI 0.74-1.12) when compared with best supportive care. Conclusions: This study comprehensively evaluated the safety and efficacy of chemotherapy or targeted therapy regimens for advanced biliary tract cancer and found 11 "moderate" or "high" levels of evidence, however, most of the evidence was still at "low" or "very low" levels. More randomized controlled studies are needed in the future to further summarize high-level evidence.

show abstract

“…Modest or even absent significant clinical activity was noted at the cost of relevant toxicities (97)(98)(99). In a meta-analysis of 6 trials involving 855 patients treated either with erlotinib, cetuximab, panitumumab, cediranib or sorafenib, no OS advantage was observed in the experimental arms despite enhanced or a trend for enhanced RR and PFS (100). As second-line agents, in a very small retrospective analysis of 13 patients refractory to GEMOX, FOLFIRI plus bevacizumab achieved a RR of 41% with a median PFS and OS of 7.6 and 14.2 months, respectively (101).…”

Section: Targeted Agentsmentioning

confidence: 99%

Second-line therapy in advanced upper gastrointestinal cancers: current status and new prospects

Saletti

Zaniboni

2018

J. Gastrointest. Oncol.

View full text Add to dashboard Cite

The prognosis of patients with advanced upper gastrointestinal cancers (UGC) remains poor. Current available systemic armamentarium is limited, and little progress has been made over the last decades. Main achievements have been obtained in first-line setting, however an increasingly proportion of patients are considered for second-line therapy, although data from randomized trials are scarce or even lacking. In this comprehensive review we examine the literature to summarize the efficacy and limitations of second-line systemic options in patients with advanced UGC, with a glimpse into the innovations.

show abstract

Efficacy and toxicities of adding molecular targeted agents to first-line chemotherapy in the treatment of advanced biliary tract cancer: a systematic review and meta-analysis

Cited by 4 publications

References 28 publications

The HER3 pathway as a potential target for inhibition in patients with biliary tract cancers

The HER3 pathway as a potential target for inhibition in patients with biliary tract cancers

Chemotherapy and targeted therapy for advanced biliary tract cancers：An umbrella review

Second-line therapy in advanced upper gastrointestinal cancers: current status and new prospects

Contact Info

Product

Resources

About