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.
| Original language | English |
|---|---|
| Pages (from-to) | 78-88 |
| Number of pages | 11 |
| Journal | European Journal of Cancer |
| Volume | 106 |
| DOIs | |
| Publication status | Published - 2019 Jan 1 |
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Keywords
- Fluorouracil
- Leucovorin
- Pancreatic cancer
- S-1
- Second-line chemotherapy
- TAS-118
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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). / 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.
In: European Journal of Cancer, Vol. 106, 01.01.2019, p. 78-88.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer
T2 - a randomised, open-label, phase 3 study (GRAPE trial)
AU - Ioka, Tatsuya
AU - Ueno, Makoto
AU - Ueno, Hideki
AU - Park, Joon Oh
AU - Chang, Heung Moon
AU - Sasahira, Naoki
AU - Kanai, Masashi
AU - Chung, Ik Joo
AU - Ikeda, Masafumi
AU - Nakamori, Shoji
AU - Mizuno, Nobumasa
AU - Omuro, Yasushi
AU - Yamaguchi, Taketo
AU - Hara, Hiroki
AU - Sugimori, Kazuya
AU - Furuse, Junji
AU - Maguchi, Hiroyuki
AU - Furukawa, Masayuki
AU - Fukuzawa, Kengo
AU - Kim, Jun Suk
AU - Yukisawa, Seigo
AU - Takeuchi, Masahiro
AU - Okusaka, Takuji
AU - Boku, Narikazu
AU - Hyodo, Ichinosuke
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - Fluorouracil
KW - Leucovorin
KW - Pancreatic cancer
KW - S-1
KW - Second-line chemotherapy
KW - TAS-118
UR - http://www.scopus.com/inward/record.url?scp=85056895259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056895259&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2018.10.004
DO - 10.1016/j.ejca.2018.10.004
M3 - Article
C2 - 30471651
AN - SCOPUS:85056895259
VL - 106
SP - 78
EP - 88
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -