Cancer Res Treat.  2025 Apr;57(2):519-527. 10.4143/crt.2024.652.

Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-analysis Based on Individual Patient-Level Data of Randomized Trials

• Hyung J
• Kang M
• Kim I
• Kim Kp
• Ryoo BY
• Cheon J
• Ryu H
• Lee JS
• Kim JW
• Choi IS
• Park JH
• Abou-Alfa GK
• Kim JW
• Yoo C

• KMID: 2566868
• DOI: http://doi.org/10.4143/crt.2024.652

Abstract

Purpose
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Keyword

Biliary tract neoplasms; Fluoropyrimidine; Liposomal irinotecan

Figure

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  Fig. 1. Study flow. AoV, ampulla of Vater; ECOG PS, Eastern Cooperative Oncology Group performance status; mFOLFIRI, modified fluorouracil and leucovorin plus irinotecan; mFOLFOX, modified fluorouracil and leucovorin plus oxaliplatin; nal-IRI, nanoliposomal irinotecan; SNUBH, Seoul National University Bundang Hospital; 5-FU/LV, fluorouracil and leucovorin.

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  Fig. 2. Kaplan-Meier estimates of survival outcomes in the nanoliposomal irinotecan (nal-IRI) plus fluorouracil and leucovorin (5-FU/LV), modified fluorouracil and leucovorin plus oxaliplatin (mFOLFOX), modified fluorouracil and leucovorin plus irinotecan (mFOLFIRI), and 5-FU/LV groups. (A) Progression-free survival (PFS). (B) Overall survival (OS). CI, confidence interval.

Reference

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