臨床研究等提出・公開システム

A RANDOMIZED PHASE III STUDY OF TAS-118 VERSUS S-1 IN PATIENTS WITH GEMCITABINE-REFRACTORY ADVANCED PANCREATIC CANCER

GRAPE

603

The median age was 65.0 years (range, 30-79) in the TAS-118 arm and 64.0 years (range, 32-79) in the S-1 arm. The median BSA was 1.590 (range, 1.16-2.11) in the TAS-118 arm and 1.580 (range, 1.15-1.93) in the S-1 arm.

Between July 2013 and August 2015, 603 patients were randomised to TAS-118 (n= 301) or S-1 (n= 302), and 296 patients in the TAS-118 group and 290 in the S-1 group were included in the full analysis set.

Any AEs were reported in 300 patients (100.0%) in the TAS-118 arm and 293 patients (97.3%) in the S-1 arm. SAEs were reported 137 patients (45.7%), 220 events in the TAS-118 arm and 123 patients (40.9%), 206 events in the S-1 arm. The most common AEs in the TAS-118 group were decreased appetite (58.0%), stomatitis (50.3%) and diarrhea (48.7%), and those in the S-1 group were decreased appetite (54.8%), diarrhoea (42.5%) and nausea (40.5%). The numbers of patients who discontinued the study treatment due to AEs were 26 (8.7%) and 29 (9.6%) in the TAS-118 and S-1 groups, respectively. Dose reduction due to AEs was reported in 108 (36.0%) and 45 (15.0%) patients from the TAS-118 and S-1 groups, respectively. AEs leading to death were observed in 16 (5.3%) and 12 (4.0%) patients from the TAS-118 and S-1 groups, respectively; only one event (hepatic dysfunction) in the TAS-118 group was judged to be treatment related.

The median OS was 7.6 months (95% CI, 7.0-8.2) in the TAS-118 arm and 7.9 months (95% CI, 7.0-8.4) in the S-1 arm (HR, 0.98 [95% CI, 0.82-1.16]; stratified logrank test, p=0.756). No significant differences were found between the two arms.

PFS was significantly longer in the TAS-118 arm than the S-1 arm; 3.9 months (95% CI, 2.8-4.2) in the TAS-118 arm and 2.8 months (95% CI, 2.7-2.9) in the S-1 arm (HR, 0.80 [95% CI, 0.67-0.95]; p=0.009). TTF was statistically significantly longer in the TAS-118 arm than the S-1 arm; 3.0 months (95% CI, 2.8-4.0) in the TAS-118 arm and 2.8 months (95% CI, 2.5-2.8) in the S-1 arm (HR, 0.80 [95% CI, 0.68-0.95]; p=0.009). Overall, there were no significant differences in ORR or DCR between the two arms; ORR was 20.6% (95% CI, 15.7-26.1) in the TAS-118 arm and 15.1% (95% CI, 10.8-20.3) in the S-1 arm (p=0.127), and DCR was 67.2% (95% CI, 61.0-72.9) in the TAS-118 arm and 59.2% (95% CI, 52.7-65.5) in the S-1 arm (p=0.075). DR was similar in the two arms; 4.2 months (95% CI, 3.0-5.5) in the TAS-118 arm and 4.7 months (95% CI, 4.2-5.6) in the S-1 arm (HR, 0.98 [95% CI, 0.61-1.59]; p=0.992).

TAS-118 did not improve OS in patients with gemcitabine-refractory advanced pancreatic cancer compared to S-1. PFS and TTF were statistically significantly improved by TAS-118 compared with S-1. Incidence, profile and severity of adverse events were similar between groups.

Nov. 22, 2018

https://www.sciencedirect.com/science/article/pii/S0959804918314321?via%3Dihub

Undecided

https://www.clinicaltrials.jp/file/MVWZTkpWc

Taiho Pharmaceutical Co., Ltd.

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toiawaseCD1@taiho.co.jp

Taiho Pharmaceutical Co., Ltd.

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toiawase@taiho.co.jp

completed

July. 12, 2013

Interventional

A randomised, open-label study

treatment purpose

3

-Invasive pancreatic ductal carcinoma.
-Refractory to gemcitabine, and no post treatment after gemcitabine.
-Has evaluable metastatic lesion(s).
-Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1.
-Capable of oral intake.
-Written consent to participate as a subject in this clinical study.

-Unmanageable Diarrhea.
-Current or past severe lung disease.
-Any other active illness such as severe (e.g. grade 3 or higher) cardiac disease.
-The diabetic patients who have poorly controlled despite the medication or severe diabetic complication.
-Grade 3 or higher serious complications.

Both

pancreatic cancer

investigational material(s)
Generic name etc : TAS-118
INN of investigational material : -
Therapeutic category code : 42- Antineoplastic agents
Dosage and Administration for Investigational material : TAS-118 (30-60 mg) will be administered PO BID from Day 1 through Day 7 followed by a recovery period from Day 8 through Day 14. This regimen is to be repeated every 2 weeks.

control material(s)
Generic name etc : S-1
INN of investigational material : Tegafur, gimeracil, oteracil
Therapeutic category code : 422 Antimetabolic agents
Dosage and Administration for Investigational material : S-1 (40-60 mg) will be administered PO BID from Day 1 through Day 28 followed by a recovery period from Day 29 through Day 42. This regimen is to be repeated every 6 weeks.

efficacy
Overall survival

safety
efficacy
Progression free survival, Efficacy, Safety

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July. 31, 2013