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

Keisuke Miwa¹Reina Kawasaki²Mototsugu Shimokawa^3,4Taiga Otsuka⁵Tanaka Toshimitsu⁶Masaru Fukahori⁶Taro Shibuki^7,8Junichi Nakazawa⁹Shiho Arima¹⁰Futa Koga¹¹Yujiro Ueda¹²Yoshihito Kubotsu¹³Hozumi Shimokawa^14,15Shigeyuki Takeshita¹⁶Kazuo Nishikawa¹⁷Azusa Komori^17,18Satoshi Otsu¹⁷Ayumu Hosokawa¹⁹Tatsunori Sakai²⁰Hisanobu Oda²¹Machiko Kawahira²²Shuji Arita²³Takuya Honda²⁴Hiroki Taguchi^25,26Kengo Tsuneyoshi²⁵Toshihiro Fujita²⁷Takahiro Sakae²⁷Yasunori Kawaguchi²⁸Tsuyoshi Shirakawa^29,30*Toshihiko Mizuta³¹Kenji Mitsugi³²

• ¹Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kuurme, Fukuoka, Japan
• ²Division of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
• ³Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube-shi, Yamaguchi, Japan
• ⁴Clinical Research Institute, National Kyushu Cancer Center, Fukuoka-shi, Fukuoka, Fukuoka-shi, Fukuoka, Japan
• ⁵Department of Internal Medicine, Minato Medical Clinic, Fukuoka-shi, Fukuoka, Japan, Fukuoka-shi, Fukuoka, Japan
• ⁶Multidisciplinary Treatment Cancer Center, Kurume University Hospital, Kurume, Fukuoka, Japan
• ⁷Department for the Promotion of Drug and Diagnostic Development, Division of Drug and Diagnostic Development Promotion, Translational Research Support Office, National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan
• ⁸Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan
• ⁹Department of Medical Oncology, Kagoshima City Hospital, Kagoshima-shi, Kagoshima, Japan
• ¹⁰Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima-shi, Kagoshima, Japan
• ¹¹Department of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, Saga-shi, Saga, Japan
• ¹²Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, Kumamoto-shi, Kumamoto, Japan
• ¹³Department of Internal Medicine, Karatsu Red Cross Hospital, Karatsu-shi, Saga, Japan
• ¹⁴Department of Hematology Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu-shi, Fukuoka, Japan
• ¹⁵Department of Medical Oncology, Hamanomachi Hospital, Fukuoka-shi, Fukuoka, Japan
• ¹⁶Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki-shi, Nagasaki, Japan
• ¹⁷Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan
• ¹⁸Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama-shi, Ehime, Japan
• ¹⁹Department of Clinical Oncology, University of Miyazaki Hospital, Miyazaki-shi, Miyazaki, Japan
• ²⁰Department of Medical Oncology, NHO Kumamoto Medical Center, Kumamoto-shi, Kumamoto, Japan
• ²¹Division of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto-shi, Kumamoto, Japan
• ²²Department of Gastroenterology, Kagoshima Kouseiren Hospital, Kagoshima-shi, Kagoshima, Japan
• ²³Department of Chemotherapy, Miyazaki Prefectural Miyazaki Hospital, Miyazaki-shi, Miyazaki, Japan
• ²⁴Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki-shi, Nagasaki, Japan
• ²⁵Department of Gastroenterology, Izumi General Medical Center, Izumi-shi, Kagoshima, Japan
• ²⁶Department of Gastroenterology, Kagoshima City Hospital, Kagoshima-shi, Kagoshima, Japan
• ²⁷Department of Gastroenterology, Saiseikai Sendai Hospital, Satsumasendai-shi, Kagoshima, Japan
• ²⁸Department of Gastroenterology, Asakura Medical Association Hospital, Asakura-shi, Fukuoka, Japan
• ²⁹Clinical Hematology Oncology Treatment Study Group, Fukuoka-shi, Fukuoka, Japan
• ³⁰Department of Medical Checkup Center, Eikoh Hospital, Kasuya-gun, Fukuoka, Japan
• ³¹Department of Internal Medicine, Fujikawa Hospital, Saga-shi, Saga, Japan
• ³²Department of Medical Oncology, Sasebo Kyosai Hospital, Sasebo-shi, Nagasaki, Japan

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).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.