脂质体伊立替康联合5-氟尿嘧啶/亚叶酸钙对比S-1治疗吉西他滨难治性转移性胰腺癌的疗效：一项使用治疗权重逆概率的真实世界研究
Efficacy of liposomal irinotecan + 5-FU/LV vs. S-1 in gemcitabine-refractory metastatic pancreatic cancer: a real-world study using inverse probability of treatment weighting.
作者信息
Imaoka Hiroshi, Ikeda Masafumi, Kobayashi Satoshi, Ohba Akihiro, Ueno Masayuki, Suzuki Yuko, Tsumura Hidetaka, Kimura Nana, Kawaguchi Shinya, Kawamoto Yasuyuki, Nakachi Kohei, Tsuji Kunihiro, Kobayashi Noritoshi, Ashida Reiko, Okano Naohiro, Umemoto Kumiko, Murohisa Gou, Hosokawa Ayumu, Asagi Akinori, Nebiki Hiroko, Suzuki Rei, Terashima Takeshi, Shibata Ryusuke, Kawata Kazuhito, Doi Toshifumi, Ohyama Hiroshi, Kitano Yohei, Shioji Kazuhiko, Okuyama Hiroyuki, Naganuma Atsushi, Negoro Yuji, Sakamoto Yasunari, Shimizu Satoshi, Morizane Chigusa, Ueno Makoto, Furuse Junji, Nagano Hiroaki
机构信息
Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
出版信息
J Gastroenterol. 2025 Mar;60(3):356-367. doi: 10.1007/s00535-024-02186-9. Epub 2024 Nov 30.
BACKGROUND
S-1 monotherapy had previously been widely used as a second-line treatment for pancreatic cancer (PC) after gemcitabine-based chemotherapy mainly in Japan. Based on the results of the NAPOLI-1 trial, the recommended second-line therapy is now liposomal irinotecan plus fluorouracil/folinic acid (nal-IRI + 5-FU/LV). However, there have been no studies comparing nal-IRI + 5-FU/LV therapy with S-1 monotherapy.
METHODS
The main objective of this study was to compare overall survival (OS) in patients treated with nal-IRI + 5-FU/LV and those treated with S-1 monotherapy as second-line treatments, using the inverse probability of treatment weighting (IPTW) method. This study was conducted in 31 institutions participating in Japan Oncology Network in Hepatobiliary and Pancreas. To minimize potential biases due to the retrospective design, IPTW analysis was performed with multiple imputation, and imputed IPTW-adjusted hazard ratios and corresponding 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model and combined into pooled estimates.
RESULTS
A total of 463 metastatic PC patients were enrolled in this study (257 in the S-1 monotherapy group and 206 in the nal-IRI + 5-FU/LV group). The median OS was 7.50 months (95% CI 4.18-12.69 months) in the nal-IRI + 5-FU/LV group and 5.72 months (95% CI 2.76-10.79 months) in the S-1 monotherapy group. In the IPTW-adjusted Cox proportional hazards model, nal-IRI + 5-FU/LV was associated with a significant OS benefit (pooled IPTW-adjusted hazard ratio, 0.779; 95% CI 0.399-0.941; p = 0.025).
CONCLUSION
These findings support the use of nal-IRI + 5-FU/LV as standard second-line treatment for PC patients after gemcitabine-based chemotherapy.
背景
S-1单药疗法此前在日本主要作为吉西他滨化疗后胰腺癌（PC）的二线治疗方法被广泛应用。基于NAPOLI-1试验的结果，目前推荐的二线治疗方案是脂质体伊立替康联合氟尿嘧啶/亚叶酸（nal-IRI + 5-FU/LV）。然而，尚无研究比较nal-IRI + 5-FU/LV疗法与S-1单药疗法。
方法
本研究的主要目的是采用治疗权重逆概率（IPTW）方法比较接受nal-IRI + 5-FU/LV治疗的患者和接受S-1单药疗法作为二线治疗的患者的总生存期（OS）。本研究在31家参与日本肝胆胰肿瘤网络的机构中进行。为尽量减少回顾性设计导致的潜在偏倚，采用多重填补法进行IPTW分析，并使用Cox比例风险模型估计填补后的IPTW调整风险比及相应的95%置信区间（CI），并合并为汇总估计值。
结果
本研究共纳入463例转移性PC患者（S-1单药疗法组257例，nal-IRI + 5-FU/LV组206例）。nal-IRI + 5-FU/LV组的中位OS为7.50个月（95%CI 4.18 - 12.69个月），S-1单药疗法组为5.72个月（95%CI 2.76 - 10.79个月）。在IPTW调整的Cox比例风险模型中，nal-IRI + 5-FU/LV与显著的OS获益相关（汇总IPTW调整风险比为0.779；95%CI 0.399 - 0.941；p = 0.025）。
结论
这些研究结果支持将nal-IRI + 5-FU/LV作为吉西他滨化疗后PC患者的标准二线治疗方案。
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