Real‑world treatment outcomes among patients with metastatic pancreatic cancer in Japan: The Tokushukai real‑world data project

Shimoyama,Rai; Imamura,Yoshinori; Uryu,Kiyoaki; Mase,Takahiro; Fujimura,Yoshiaki; Hayashi,Maki; Ohtaki,Megu; Ohtani,Keiko; Shinozaki,Nobuaki; Minami,Hironobu

doi:10.3892/mco.2023.2694

Real‑world treatment outcomes among patients with metastatic pancreatic cancer in Japan: The Tokushukai real‑world data project

Authors:
- Rai Shimoyama
- Yoshinori Imamura
- Kiyoaki Uryu
- Takahiro Mase
- Yoshiaki Fujimura
- Maki Hayashi
- Megu Ohtaki
- Keiko Ohtani
- Nobuaki Shinozaki
- Hironobu Minami
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Affiliations: Department of General Surgery, Shonan Kamakura General Hospital, Kamakura, Kanagawa 247‑8533, Japan, Department of Medical Oncology and Hematology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan, Department of Medical Oncology, Yao Tokushukai General Hospital, Yao, Osaka 581‑0011, Japan, Department of Breast Surgery, Ogaki Tokushukai Hospital, Ogaki, Gifu 503‑0015, Japan, Tokushukai Information System, Inc., Osaka 530‑0001, Japan, Mirai Iryo Research Center Inc., Tokyo 102‑0074, Japan, deCult Co., Ltd., Hatsukaichi, Hiroshima 739‑0413, Japan
Published online on: October 25, 2023 https://doi.org/10.3892/mco.2023.2694
Article Number: 98
Copyright: © Shimoyama et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate temporal trends in treatment patterns and prognostic factors for overall survival (OS) among patients with metastatic pancreatic cancer. From the Tokushukai REAl‑world Data project, 1,093 patients with metastatic pancreatic cancer treated with gemcitabine, tegafur/gimeracil/oteracil (S‑1), gemcitabine plus S‑1, gemcitabine plus nab‑paclitaxel, or fluorouracil, folic acid, oxaliplatin and irinotecan (FOLFIRINOX) between April 2010 and March 2020 were identified. Stratified/conventional Cox regression analyses were conducted to examine associations between patient‑ and tumor‑related factors, study period, hospital volume, hospital type and first‑line chemotherapy regimens. Overall, 846 patients were selected (503 male patients; median age, 70 years) after excluding ineligible patients. Over a median follow‑up of 5.4 months, the median OS was 6.8 months (95% confidence interval, 6.3‑7.4). The median OS for gemcitabine, S‑1, gemcitabine plus S‑1, gemcitabine plus nab‑paclitaxel and FOLFIRINOX regimens was 5.9, 5.3, 7.7, 9.0 and 9.5 months, respectively. The median OS for 2010‑2013, 2014‑2017 and 2017‑2020 was 6.2, 7.1 and 7.8 months, respectively. Performance status, body mass index and first‑line chemotherapy regimens were identified to be significant prognostic factors. In summary, the real‑world data indicated that standard care, including chemotherapy, for metastatic pancreatic cancer was widely used in hospitals throughout Japan and verified the survival benefits of gemcitabine plus nab‑paclitaxel and FOLFIRINOX observed in prior clinical trials. This trial has been registered in the University Hospital Medical Information Network Clinical Trials Registry as UMIN000050590 on April 1, 2023.

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1	Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2021. CA Cancer J Clin. 71:7–33. 2021.PubMed/NCBI View Article : Google Scholar
2	Cancer statistics. https://ganjoho.jp/reg_stat/statistics/data/dl/en.html. Accessed June 30 2022 Cancer Information Service, Natl Cancer Cntr, Japan. Vital Statistics of Japan Ministry of Health, Labour and Welfare.
3	Ben Q, Xu M, Ning X, Liu J, Hong S, Huang W, Zhang H and Li Z: Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies. Eur J Cancer. 47:1928–1937. 2011.PubMed/NCBI View Article : Google Scholar
4	Stolzenberg-Solomon RZ, Adams K, Leitzmann M, Schairer C, Michaud DS, Hollenbeck A, Schatzkin A and Silverman DT: Adiposity, physical activity, and pancreatic cancer in the National Institutes of Health-AARP Diet and Health Cohort. Am J Epidemiol. 167:586–597. 2008.PubMed/NCBI View Article : Google Scholar
5	Aune D, Greenwood DC, Chan DS, Vieira R, Vieira AR, Navarro Rosenblatt DA, Cade JE, Burley VJ and Norat T: Body mass index, abdominal fatness and pancreatic cancer risk: A systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol. 23:843–852. 2012.PubMed/NCBI View Article : Google Scholar
6	Matsuo K, Ito H, Wakai K, Nagata C, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Sasazuki S, Inoue M, et al: Cigarette smoking and pancreas cancer risk: An evaluation based on a systematic review of epidemiologic evidence in the Japanese population. Jpn J Clin Oncol. 41:1292–1302. 2011.PubMed/NCBI View Article : Google Scholar
7	Tramacere I, Scotti L, Jenab M, Bagnardi V, Bellocco R, Rota M, Corrao G, Bravi F, Boffetta P and La Vecchia C: Alcohol drinking and pancreatic cancer risk: A meta-analysis of the dose-risk relation. Int J Cancer. 126:1474–1486. 2010.PubMed/NCBI View Article : Google Scholar
8	Raimondi S, Lowenfels AB, Morselli-Labate AM, Maisonneuve P and Pezzilli R: Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol. 24:349–358. 2010.PubMed/NCBI View Article : Google Scholar
9	Burris HA III, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, et al: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. J Clin Oncol. 15:2403–2413. 1997.PubMed/NCBI View Article : Google Scholar
10	Ueno H, Okusaka T, Ikeda M, Takezako Y and Morizane C: An early phase II study of S-1 in patients with metastatic pancreatic cancer. Oncology. 68:171–178. 2005.PubMed/NCBI View Article : Google Scholar
11	Okusaka T, Funakoshi A, Furuse J, Boku N, Yamao K, Ohkawa S and Saito H: A late phase II study of S-1 for metastatic pancreatic cancer. Cancer Chemother Pharmacol. 61:615–621. 2008.PubMed/NCBI View Article : Google Scholar
12	Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, et al: Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 25:1960–1966. 2007.PubMed/NCBI View Article : Google Scholar
13	Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, et al: Folfirinox versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 364:1817–1825. 2011.PubMed/NCBI View Article : Google Scholar
14	Okusaka T, Ikeda M, Fukutomi A, Ioka T, Furuse J, Ohkawa S, Isayama H and Boku N: Phase II study of FOLFIRINOX for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. Cancer Sci. 105:1321–1326. 2014.PubMed/NCBI View Article : Google Scholar
15	Ozaka M, Ishii H, Sato T, Ueno M, Ikeda M, Uesugi K, Sata N, Miyashita K, Mizuno N, Tsuji K, et al: A phase II study of modified folfirinox for chemotherapy-naïve patients with metastatic pancreatic cancer. Cancer Chemother Pharmacol. 81:1017–1023. 2018.PubMed/NCBI View Article : Google Scholar
16	Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, et al: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 369:1691–1703. 2013.PubMed/NCBI View Article : Google Scholar
17	Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, et al: Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 31:1640–1648. 2013.PubMed/NCBI View Article : Google Scholar
18	National Comprehensive Cancer Network (NCCN): NCCN clinical practice guidelines in oncology pancreatic adenocarcinoma. Version 1.2022. https://www.nccn.org/guidelines/category_1. Accessed June 30, 2022.
19	Okusaka T, Nakamura M, Yoshida M, Kitano M, Uesaka K, Ito Y, Furuse J, Hanada K and Okazaki K: Committee for Revision of Clinical Guidelines for Pancreatic Cancer of the Japan Pancreas Society. Clinical practice guidelines for pancreatic cancer 2019 from the Japan Pancreas Society: A synopsis. Pancreas. 49:326–335. 2020.PubMed/NCBI View Article : Google Scholar
20	Wang-Gillam A, Hubner RA, Siveke JT, Von Hoff DD, Belanger B, de Jong FA, Mirakhur B and Chen LT: NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors. Eur J Cancer. 108:78–87. 2019.PubMed/NCBI View Article : Google Scholar
21	Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, et al: Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 381:317–327. 2019.PubMed/NCBI View Article : Google Scholar
22	Averitt AJ, Weng C, Ryan P and Perotte A: Translating evidence into practice: Eligibility criteria fail to eliminate clinically significant differences between real-world and study populations. NPJ Digit Med. 3(67)2020.PubMed/NCBI View Article : Google Scholar
23	Hilgers RD, König F, Molenberghs G and Senn S: Design and analysis of clinical trials for small rare disease populations. J Rare Dis Res Treat. 1:53–60. 2016.
24	Latimer NR: Survival analysis for economic evaluations alongside clinical trials-extrapolation with patient-level data: Inconsistencies, limitations, and a practical guide. Med Decis Making. 33:743–754. 2013.PubMed/NCBI View Article : Google Scholar
25	Corrigan-Curay J, Sacks L and Woodcock J: Real-world evidence and real-world data for evaluating drug safety and effectiveness. JAMA. 320:867–868. 2018.PubMed/NCBI View Article : Google Scholar
26	Katkade VB, Sanders KN and Zou KH: Real world data: An opportunity to supplement existing evidence for the use of long-established medicines in health care decision making. J Multidiscip Healthc. 11:295–304. 2018.PubMed/NCBI View Article : Google Scholar
27	Makady A, de Boer A, Hillege H, Klungel O and Goettsch W: (on behalf of GetReal Work Package 1). What is real-world data? A review of definitions based on literature and stakeholder interviews. Value Health. 20:858–865. 2017.PubMed/NCBI View Article : Google Scholar
28	Shimoyama R, Imamura Y, Uryu K, Mase T, Fujimura Y, Hayashi M, Ohtaki M, Ohtani K, Shinozaki N and Minami H: Real-world outcomes of systemic therapy in Japanese patients with cancer (Tokushukai REAl-world Data project: TREAD): Study protocol for a nationwide cohort study. Healthcare (Basel). 10(2146)2022.PubMed/NCBI View Article : Google Scholar
29	National Cancer Registry (Ministry of Health, Labour and Welfare) tabulated by Cancer Information Service, National Cancer Center, Japan. https://ganjoho.jp/med_pro/cancer_control/can_reg/index.html. Accessed June 30, 2022.
30	Haj Mohammad N, Bernards N, Besselink MG, Busch OR, Wilmink JW, Creemers GJ, De Hingh IH, Lemmens VE and van Laarhoven HW: Volume matters in the systemic treatment of metastatic pancreatic cancer: A population-based study in the Netherlands. J Cancer Res Clin Oncol. 142:1353–1360. 2016.PubMed/NCBI View Article : Google Scholar
31	Terashima T, Yamashita T, Sakai A, Ohta H, Hinoue Y, Toya D, Kawai H, Yonejima M, Urabe T, Noda Y, et al: Treatment patterns and outcomes of unresectable pancreatic cancer patients in real-life practice: A region-wide analysis. Jpn J Clin Oncol. 48:966–973. 2018.PubMed/NCBI View Article : Google Scholar
32	Sasaki T, Kanata R, Yamada I, Matsuyama M, Ozaka M and Sasahira N: Improvement of treatment outcomes for metastatic pancreatic cancer: A real-world data analysis. In Vivo. 33:271–276. 2019.PubMed/NCBI View Article : Google Scholar
33	Javed MA, Beyer G, Le N, Vinci A, Wong H, Palmer D, Morgan RD, Lamarca A, Hubner RA, Valle JW, et al: Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe. Pancreatology. 19:97–104. 2019.PubMed/NCBI View Article : Google Scholar
34	Cho IR, Kang H, Jo JH, Lee HS, Chung MJ, Park JY, Park SW, Song SY, An C, Park MS and Bang S: Folfirinox vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study. World J Gastrointest Oncol. 12:182–194. 2020.PubMed/NCBI View Article : Google Scholar
35	Chan KKW, Guo H, Cheng S, Beca JM, Redmond-Misner R, Isaranuwatchai W, Qiao L, Earle C, Berry SR, Biagi JJ, et al: Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: A population-based propensity score-weighted analysis. Cancer Med. 9:160–169. 2020.PubMed/NCBI View Article : Google Scholar
36	Franco F, Camara JC, Martín-Valadés JI, López-Alfonso A, Marrupe D, Gutiérrez-Abad D, Martínez-Amores B, León A, Juez I, Pérez M, et al: Clinical outcomes of folfirinox and gemcitabine-nab paclitaxel for metastatic pancreatic cancer in the real world setting. Clin Transl Oncol. 23:812–819. 2021.PubMed/NCBI View Article : Google Scholar
37	Pijnappel EN, Dijksterhuis WPM, van der Geest LG, de Vos-Geelen J, de Groot JWB, Homs MYV, Creemers GJ, Mohammad NH, Besselink MG, van Laarhoven HWM, et al: First- and second-line palliative systemic treatment outcomes in a real-world metastatic pancreatic cancer cohort. J Natl Compr Canc Netw. 20:443–450.e3. 2021.PubMed/NCBI View Article : Google Scholar
38	Mizusawa J, Ohba A, Ozaka M, Katayama H, Okusaka T, Kobayashi S, Ikeda M, Terashima T, Sasahira N, Okano N, et al: Protocol of a randomized phase II/III study of gemcitabine plus nab-paclitaxel combination therapy versus modified FOLFIRINOX versus S-IROX for metastatic or recurrent pancreatic cancer: JCOG1611 (GENERATE). Jpn J Clin Oncol. 53:80–84. 2023.