Efficacy and Toxicity of Pemigatinib in Advanced Cholangiocarcinoma Harboring FGFR Fusions or Rearrangements: A Systematic Review and Meta-analysis.

BACKGROUND

The efficacy and safety of pemigatinib in advanced cholangiocarcinoma (aCCA) were presented in phase I-II trials and retrospective reports, with small sample sizes and variable results.

METHODS

A systematic literature search included studies investigating the efficacy/safety of pemigatinib in aCCA harboring FGFR fusions/rearrangements. Primary outcomes were objective response rate (ORR) and treatment-related adverse events (AEs). A pooled proportion meta-analysis was performed.

RESULTS

Three hundred and twenty-seven patients in eight studies were included (three phase-II, one phase-I/II, two phase-I, and two retrospective). In the pooled analyses, the median age was 58.9 years (95% confidence interval (CI): 51.9-65.8); 33.4% (95% CI: 28.1-39.0) were male. Pemigatinib was the second-line treatment in 58.5% (95% CI: 52.7-64.1) and was beyond second-line in the remaining. ORR was 42.2% (95% CI: 35.9-48.7) (I:48.4%) and disease control rate (DCR) was 86.5% (95% CI: 81.6-90.5) (I: 58.8%). Median progression-free survival (PFS) was 7.8 months (95% CI: 6.2-9.4) (I: 11.6%). Two studies reported overall survival (OS) (median 17.5 and 17.1 months). The most common AEs (any grade) were hyperphosphatemia (46%), dysgeusia (33.2%), alopecia (31.4%), fatigue (30.9%), stomatitis (28.5%), and diarrhea (27.5%). Cumulative eye and nail toxicities were observed in 32.5% and 40.9%, and retinal detachment in 5.5%.

CONCLUSION

This analysis emphasizes the FGFR alteration testing and pemigatinib use in the second-line and beyond treatment of aCCA.

REGISTRATION ID (PROSPERO)

CRD42024627459.

© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.