Systematic review and first meta-analysis of the efficacy and safety of gemcitabine-cisplatin combined with paclitaxel in patients with advanced biliary tract cancer.

BACKGROUND

Advanced biliary tract cancer (BTC) has a poor prognosis with limited options. Gemcitabine–cisplatin (Gem/Cis) is standard first-line therapy, but outcomes remain suboptimal. This meta-analysis evaluated the efficacy and safety of adding paclitaxel complex to Gem/Cis (Gem/Cis/P) in advanced BTC.

METHODS

The PROSPERO-registered protocol (CRD420251177440) guided searches of PubMed, EMBASE, Cochrane Library, and Web of Science for clinical studies on Gem/Cis/P in BTC. Three reviewers independently selected studies, extracted data, and assessed quality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a fixed-effects model when heterogeneity was low (I² ≤ 50% and p ≥ 0.1), otherwise a random-effects model was applied. All analyses were conducted with RevMan 5.3.

RESULTS

Ten studies (1,401 patients) were included; four controlled studies (739 patients) were meta-analyzed. Compared with Gem/Cis, Gem/Cis/P significantly improved response rates: objective response rate (OR = 1.51; 95% CI: 1.08 ~ 2.11; p = 0.02), disease control rate (OR = 1.47; 95% CI: 1.04 ~ 2.08; p = 0.03), and partial response (OR = 1.77; 95% CI: 1.1 ~ 2.62; p = 0.005). However, no significant differences were observed in overall survival (HR = 0.86; 95% CI: 0.71 ~ 1.03; p = 0.11) or progression-free survival (HR = 0.86; 95% CI: 0.73 ~ 1.02; p = 0.08). Grade ≥ 3 adverse events were significantly higher with triplet therapy (OR = 1.79; 95% CI: 1.27 ~ 2.51; p = 0.0008), particularly neutropenia (OR = 1.65; 95% CI: 1.19 ~ 2.28; p = 0.003).

CONCLUSION

Adding paclitaxel to gemcitabine–cisplatin improves response rates but not survival in advanced BTC, with increased toxicity. These findings highlight the need for careful patient selection and validation in large-scale trials.