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. 2025 Jul 17:15:1626689.
doi: 10.3389/fonc.2025.1626689. eCollection 2025.

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

Keisuke Miwa  1 , Reina Kawasaki  2 , Mototsugu Shimokawa  3   4 , Taiga Otsuka  5 , Toshimitsu Tanaka  1 , Masaru Fukahori  1 , Taro Shibuki  6   7 , Junichi Nakazawa  8 , Shiho Arima  9 , Futa Koga  10 , Yujiro Ueda  11 , Yoshihito Kubotsu  12 , Hozumi Shimokawa  13   14 , Shigeyuki Takeshita  15 , Kazuo Nishikawa  16 , Azusa Komori  16   17 , Satoshi Otsu  16 , Ayumu Hosokawa  18 , Tatsunori Sakai  19 , Hisanobu Oda  2 , Machiko Kawahira  20 , Shuji Arita  21 , Takuya Honda  22 , Hiroki Taguchi  23   24 , Kengo Tsuneyoshi  23 , Toshihiro Fujita  25 , Takahiro Sakae  25 , Yasunori Kawaguchi  26 , Tsuyoshi Shirakawa  27   28 , Toshihiko Mizuta  29 , Kenji Mitsugi  30
Affiliations

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

Keisuke Miwa et al. Front Oncol. .

Abstract

Introduction: The 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.

Methods: Between 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.

Results: Of 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).

Conclusion: Third-line CTx should be actively considered for patients with UPC, as the approach may significantly extend survival in those who can tolerate the treatment.

Keywords: best supportive care; chemotherapy; nanoliposomal irinotecan; pancreatic cancer; third-line treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of patient selection and progression. NFF, nanoliposomal irinotecan combined with fluorouracil and folinic acid; BSC, best supportive care; CTx, chemotherapy.
Figure 2
Figure 2
(A) Overall survival following second-line chemotherapy. (B) Overall survival following first-line chemotherapy. BSC, best supportive care; HR, hazard ratio; CI, confidence interval.
Figure 3
Figure 3
(A) Overall survival from the start of third-line chemotherapy. (B) Cox adjusted post-discontinuation survival after second-line chemotherapy. BSC, best supportive care; HR, hazard ratio; CI, confidence interval.
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