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

• Published in: Cancer research and treatment Vol. 57; no. 2; pp. 519 - 527
• Main Authors: Hyung, Jaewon, Kang, Minsu, Kim, Ilhwan, Kim, Kyu-pyo, Ryoo, Baek-Yeol, Cheon, Jaekyung, Ryu, Hyewon, Lee, Ji Sung, Kim, Ji-Won, Choi, In Sil, Park, Jin Hyun, Abou-Alfa, Ghassan K., Kim, Jin Won, Yoo, Changhoon
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01.04.2025; 대한암학회
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biliary Tract Neoplasms - drug therapy; Biliary Tract Neoplasms - mortality; Biliary Tract Neoplasms - pathology; Clinical Trials, Phase II as Topic; Female; Fluorouracil - administration & dosage; Fluorouracil - therapeutic use; Humans; Leucovorin - administration & dosage; Leucovorin - therapeutic use; Male; Middle Aged; Original; Randomized Controlled Trials as Topic; Treatment Outcome; 의학일반; Liposomal irinotecan; Biliary tract neoplasms; Fluoropyrimidine
• ISSN: 1598-2998; 2005-9256; 2005-9256
• DOI: 10.4143/crt.2024.652

PurposeWhile 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.