Yoo Changhoon, Saborowski Anna, Hyung Jaewon, Wenzel Patrick, Kim Ilhwan, Wege Henning, Kim Kyu-Pyo, Folprecht Gunnar, Ryoo Baek-Yeol, Schütt Phillip, Cheon Jaekyung, Götze Thorsten, Ryu Hyewon, Lee Ji Sung, Vogel Arndt
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
J Hepatol. 2025 Mar 25. doi: 10.1016/j.jhep.2025.03.013.
BACKGROUND & AIMS: Liposomal irinotecan (nal-IRI) combined with fluorouracil (5-FU)/leucovorin (LV) as a second-line treatment for biliary tract cancer (BTC) following progression on gemcitabine-based therapy yielded conflicting outcomes in the Korean NIFTY and German NALIRICC trials. This necessitated a comprehensive pooled analysis to evaluate its efficacy and safety.
Individual patient data were pooled from the intention-to-treat populations of the NIFTY and NALIRICC trials. The primary endpoint was progression-free survival (PFS).
A total of 278 patients were included: 137 in the nal-IRI plus 5-FU/LV group and 141 in the 5-FU/LV group. The nal-IRI plus 5-FU/LV group showed significantly longer median PFS (3.6 months [95% CI 2.7-4.4] vs. 1.8 months [95% CI 1.5-2.6]; hazard ratio 0.65, p <0.001). Median overall survival was 8.1 months (95% CI 6.0-8.9) and 6.1 months (95% CI 5.3-7.5), respectively (hazard ratio 0.77, p = 0.051). Objective response rates were also higher in the nal-IRI plus 5-FU/LV group than in the 5-FU/LV group (17.5% vs. 2.8%; p <0.001). Post-study irinotecan-containing therapy was administered in 4 (2.9%) and 21 (15.3%) patients in the nal-IRI plus 5-FU/LV group and 5-FU/LV group, respectively. Adverse events varied by ethnicity, with gastrointestinal toxicities more common in Germans and neutropenia more prevalent in Koreans; treatment discontinuation without disease progression occurred in 31.3% vs. 8.0%, respectively.
The addition of nal-IRI to 5-FU/LV significantly improved PFS and objective response rates, supporting its potential as subsequent-line therapy. Differences in safety profiles underscore the relevance of ethnicity for nal-IRI in patients with BTC.
Current standard of care for second-line therapy in patients with advanced biliary tract cancer (BTC) is FOLFOX. This study provides robust evidence supporting the potential role of adding liposomal irinotecan (nal-IRI) to fluorouracil and leucovorin (5-FU/LV) as a subsequent therapy for patients with BTC who have progressed on gemcitabine-based regimens. The findings demonstrate significant improvements in progression-free survival and objective response rates in a patient population for whom treatment options are limited. Furthermore, the study underscores the necessity of considering ethnic differences in adverse event profiles to optimize treatment administration and patient outcomes.
NCT03524508 and NCT03043547.
在基于吉西他滨的治疗进展后，脂质体伊立替康（nal-IRI）联合氟尿嘧啶（5-FU）/亚叶酸钙（LV）作为胆道癌（BTC）的二线治疗方案，在韩国的NIFTY试验和德国的NALIRICC试验中产生了相互矛盾的结果。因此有必要进行全面的汇总分析以评估其疗效和安全性。
从NIFTY试验和NALIRICC试验的意向性治疗人群中汇总个体患者数据。主要终点是无进展生存期（PFS）。
共纳入278例患者：nal-IRI联合5-FU/LV组137例，5-FU/LV组141例。nal-IRI联合5-FU/LV组的中位PFS显著更长（3.6个月[95%CI 2.7-4.4] vs. 1.8个月[95%CI 1.5-2.6]；风险比0.65，p<0.001）。中位总生存期分别为8.1个月（95%CI 6.0-8.9）和6.1个月（95%CI 5.3-7.5）（风险比0.77，p = 0.051）。nal-IRI联合5-FU/LV组的客观缓解率也高于5-FU/LV组（17.5% vs. 2.8%；p<0.001）。nal-IRI联合5-FU/LV组和5-FU/LV组分别有4例（2.9%）和21例（15.3%）患者在研究结束后接受了含伊立替康的治疗。不良事件因种族而异，胃肠道毒性在德国人中更常见，中性粒细胞减少在韩国人中更普遍；在无疾病进展的情况下停药的发生率分别为31.3%和8.0%。
在5-FU/LV基础上加用nal-IRI可显著改善PFS和客观缓解率，支持其作为后续治疗的潜力。安全性方面的差异凸显了种族因素对BTC患者使用nal-IRI的相关性。
晚期胆道癌（BTC）患者二线治疗的当前标准治疗方案是FOLFOX。本研究提供了有力证据，支持在氟尿嘧啶和亚叶酸钙（5-FU/LV）基础上加用脂质体伊立替康（nal-IRI）作为对基于吉西他滨方案治疗进展的BTC患者的后续治疗方案的潜在作用。研究结果表明，在治疗选择有限的患者群体中，无进展生存期和客观缓解率有显著改善。此外，该研究强调了考虑不良事件谱中的种族差异以优化治疗管理和患者预后的必要性。
NCT03524508和NCT03043547。
