The efficacy and safety of different pharmacological interventions for patients with advanced biliary tract cancer: A network meta-analysis

Abstract

Biliary tract cancer (BTC) is the second common cancer in liver cancer. Chemotherapy is the mainstay of treatments for patients with advanced or metastatic disease, while fluorouracil (FU)-based and gemcitabine (GEM)-based treatments are most widely applied. This NMA aimed to figure out whether the addition of platinum (PLA) and target agents (TAR) can influence the efficacy and safety of standard chemotherapy. Network meta-analysis (NMA) was conducted based on the records from PubMed, Embase and Cochrane. Eligible data was extracted from available qualified trials and outcomes. Software R 3.2.3 and STATA 13.0 were used to conduct the Bayesian NMA, calculating odds ratios (ORs) and hazard ratios (HRs) with 95% credible interval (CrI) to evaluate different treatments.Almost all treatments were superior to best supportive care (BSC) and FU in terms of 1-OS, 2-OS and 1-PFS. GEM+PLA and GEM+PLA+TAR exhibited better efficacy than most treatments in 1-OS, 2-OS and 1-PFS, and yielded better results than BSC and GEM+FU in terms of 2-PFS. Most drug-containing treatments reported higher overall response rate (ORR) than BSC. GEM and GEM+FU were associated with a higher risk of neutropenia and thrombocytopenia compared to FU, FU+PLA and GEM+PLA. No statistical difference was detected in terms of nausea and vomiting.GEM+PLA and GEM+PLA+TAR were both efficacious and were associated with fewer adverse events. In conclusion, the addition of PLA can significantly improve the efficacy of FU and GEM-based treatments, and the addition of TAR to GEM+PLA can contribute to further improvement, but with a mild increase of adverse events.

The Efficacy of Different Chemotherapy Regimens for Advanced Biliary Tract Cancer: A Systematic Review and Network Meta-Analysis

“…In our study, gemcitabine plus platinum regimens were generally found to obtain better efficacy than fluoropyrimidine based regimens. A previous NMA (11) came to the same conclusion that gemcitabine based regimens yielded more satisfying survival outcomes than fluoropyrimidine based. But when it came to toxicity, a gemcitabine based regimen was likely to cause neutropenia than fluoropyrimidine based regimens.…”

“…The two trials both demonstrated that GP was associated with a significant survival advantage without increasing adverse events. Fluorouracil based chemotherapy including S-1 and 5-FU is also confirmed to be an effective therapy to treat advanced BTC (9, 10) with less adverse events than gemcitabine (GEM) based (11). There are currently several trials investigating the role of molecularly targeted drugs plus gemcitabine and oxaliplatin (GEMOX) in BTCs (12–15).…”

“…No significant difference was observed in the incidences of the grade 3/4 adverse events in these two meta-analyses, but patients who received GEMOX plus EGFR-targeted chemotherapy showed higher risks of diarrhea, neutropenia, transaminase increase and a skin rash than those who were treated with GEMOX chemotherapy in the meta-analysis of four randomized control trials (RCTs). A NMA suggested that targeted agents added to GP or GEMOX achieved a superior survival outcome though associated with higher risk of adverse effects (11). A randomized phase II study conducted by Schinizari et al in 2017 suggested that 5-FU/LV plus oxaliplatin (Folfox-4) could be an option as first-line treatment with the median overall survival (OS) of 13.0 months (9), even though the regimen of 5-FU and folinic acid (FUFA) were ever considered to be less effective (18).…”

Efficacy and Safety of First-Line Chemotherapies for Patients With Advanced Biliary Tract Carcinoma: A Systematic Review and Network Meta-Analysis

“…Meanwhile, we also found that GEMOX+erlotinib was better than the protocol fluorouracil+folic acid in OS, PFS, and ORR. Both previous NMAs also suggested that protocol gemcitabine was superior to protocol fluorouracil ( 38 , 39 ). Cediranib combination chemotherapy in this NMA also has preferable ORR and tolerance.…”

“…NMA can reach the direct and indirect comparisons in RCTs, and our RCTs account for a large proportion, thus obtaining a more complete outcome data. A previous NMA has proven no statistically significant difference in toxicity between chemotherapy combined with targeted therapy and chemotherapy alone ( 38 ). By clustering the SUCRA of ORRs and AEs of each treatment, we found that targeted therapy combined with chemotherapy is in a better position in the quadrant.…”