AUTHOR=Miwa Keisuke , Kawasaki Reina , Shimokawa Mototsugu , Otsuka Taiga , Tanaka Toshimitsu , Fukahori Masaru , Shibuki Taro , Nakazawa Junichi , Arima Shiho , Koga Futa , Ueda Yujiro , Kubotsu Yoshihito , Shimokawa Hozumi , Takeshita Shigeyuki , Nishikawa Kazuo , Komori Azusa , Otsu Satoshi , Hosokawa Ayumu , Sakai Tatsunori , Oda Hisanobu , Kawahira Machiko , Arita Shuji , Honda Takuya , Taguchi Hiroki , Tsuneyoshi Kengo , Fujita Toshihiro , Sakae Takahiro , Kawaguchi Yasunori , Shirakawa Tsuyoshi , Mizuta Toshihiko , Mitsugi Kenji 

TITLE=Efficacy of third-line chemotherapy following nanoliposomal irinotecan combined with fluorouracil and folinic acid as second-line treatment for unresectable pancreatic cancer

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1626689

DOI=10.3389/fonc.2025.1626689

ISSN=2234-943X

ABSTRACT=IntroductionThe significance of third-line chemotherapy (CTx) in unresectable pancreatic cancer (UPC) remains unclear. This study evaluated the therapeutic impact of third-line CTx after nanoliposomal irinotecan and fluorouracil combined with folinic acid (nal-IRI + 5-FU/LV) therapy as second-line CTx for UPC.MethodsBetween June 2020 and May 2021, 104 patients who received nal-IRI + 5-FU/LV therapy as second-line CTx were retrospectively analyzed for post-discontinuation survival (PDS) and overall survival (OS). Comparisons were made between patients transitioning to third-line CTx and those receiving best supportive care (BSC), using a Cox proportional hazards model adjusted for patient background.ResultsOf the cohort, 34 patients received third-line CTx, whereas 61 transitioned to BSC. The median OS from first-line CTx in the third-line CTx group was 18.0 months, with a median OS of 9.7 months from second-line CTx. Adjusted median PDS following second-line CTx was 6.5 months for the third-line CTx group compared to 2.3 months for the BSC group (adjusted hazard ratio 0.16; 95% confidence interval 0.08–0.32; P < 0.01).ConclusionThird-line CTx should be actively considered for patients with UPC, as the approach may significantly extend survival in those who can tolerate the treatment.