TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer: a randomised, open-label, phase 3 study (GRAPE trial)open access
- Authors
- Ioka, Tatsuya; Ueno, Makoto; Ueno, Hideki; Park, Joon Oh; Chang, Heung-Moon; Sasahira, Naoki; Kanai, Masashi; Chung, Ik Joo; Ikeda, Masafumi; Nakamori, Shoji; Mizuno, Nobumasa; Omuro, Yasushi; Yamaguchi, Taketo; Hara, Hiroki; Sugimori, Kazuya; Furuse, Junji; Maguchi, Hiroyuki; Furukawa, Masayuki; Fukuzawa, Kengo; Kim, Jun-Suk; Yukisawa, Seigo; Takeuchi, Masahiro; Okusaka, Takuji; Boku, Narikazu; Hyodo, Ichinosuke
- Issue Date
- Jan-2019
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Pancreatic cancer; TAS-118; S-1; Leucovorin; Fluorouracil; Second-line chemotherapy
- Citation
- EUROPEAN JOURNAL OF CANCER, v.106, pp 78 - 88
- Pages
- 11
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- EUROPEAN JOURNAL OF CANCER
- Volume
- 106
- Start Page
- 78
- End Page
- 88
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/34057
- DOI
- 10.1016/j.ejca.2018.10.004
- ISSN
- 0959-8049
1879-0852
- Abstract
- Background: In our previous randomised phase 2 study for patients with gemcitabine-refractory advanced pancreatic cancer, S-1 plus leucovorin improved progression-free survival compared with S-1 alone. Here, we evaluated the efficacy of TAS-118 (S-1 plus leucovorin) versus S-1 in overall survival (OS). Patients and methods: This randomised, open-label, phase 3 study was conducted at 58 centres in Japan and Korea. Patients with metastatic pancreatic cancer that progressed during first-line gemcitabine-based chemotherapy or recurred during or after post-operative gemcitabine- based adjuvant treatment were randomly assigned (1:1) to receive either S-1 (40-60 mg, twice daily for 4 weeks in a 6-week cycle) or TAS-118 (S-1 40-60 mg plus leucovorin 25 mg, twice daily for 1 week in a 2-week cycle). The primary end-point was OS. Results: A total of 603 patients were randomised, and 300 and 301 patients received TAS-118 and S-1, respectively. There was no difference in OS between groups (median OS for TAS-118 versus S-1, 7.6 months versus 7.9 months; hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.82-1.16]; P = 0.756). Progression-free survival was significantly longer with TAS-118 than S-1 (median, 3.9 months versus 2.8 months; HR, 0.80 [95% CI, 0.67-0.95]; P = 0.009). There were interactions between Japan and Korea (P = 0.004) and between unresectable and recurrent disease (P = 0.025) in OS. Incidence, profile and severity of adverse events were similar between groups. Conclusion: TAS-118 did not improve OS in patients with gemcitabine-refractory advanced pancreatic cancer compared to S-1. Further studies are needed to find patients who have benefit from adding leucovorin to S-1. (C) 2018 The Authors. Published by Elsevier Ltd.
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Collections - 2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
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