639P - The final results of a multicenter phase II study of TAS-102 monotherapy in patients with pre-treated advanced gastric cancer (EPOC1201)

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Anticancer agents
Gastric Cancer
Therapy
Biological Therapy
Presenter Hideaki Bando
Citation Annals of Oncology (2016) 27 (6): 207-242. 10.1093/annonc/mdw371
Authors H. Bando1, T. Doi2, K. Muro3, H. Yasui4, T. Nishina5, K. Yamaguchi6, S. Takahashi7, H. Hasegawa8, S. Nomura8, H. Kuno9, K. Shitara1, A. Sato8, A. Ohtsu1
  • 1Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 3Department Of Clinical Oncology, Aichi Cancer Center Hospital, 464-0021 - Nagoya/JP
  • 4Division Of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka/JP
  • 5Department Of Gastrointestinal Medical Oncology, Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 6Department Of Gastroenterological Chemotherapy, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 7Department Of Medical Oncology, Cancer Institute Hospital of JFCR, Tokyo/JP
  • 8Office Of Clinical Research Support, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 9Department Of Diagnostic Radiology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP

Abstract

Background

American phase I studies have reported that the recommended dose of TAS-102 (trifluridine/tipiracil) was 25 mg/m2 b.i.d., although this schedule did not provide clinically relevant improvements in a phase II study of advanced gastric cancer (AGC). However, a pivotal phase III study revealed that TAS-102 at 35 mg/m2 b.i.d. provided a clinically relevant improvement in overall survival among patients with metastatic colorectal cancer. Thus, we re-evaluated the efficacy, safety, and pharmacokinetic (PK) parameters of TAS-102 at 35 mg/m2 b.i.d. in patients with AGC. In an expanded cohort, we also evaluated the safety and PK parameters of a 40 mg/m2 b.i.d. schedule.

Methods

All patients had undergone one or two previous chemotherapy regimens that contained fluoropyrimidine, platinum agents, and taxanes or irinotecan. In this study, we assessed the investigator-determined and the independent central review's disease control rate (DCR), response rate, progression-free survival (PFS), overall survival (OS), safety profiles, and PK profiles.

Results

Twenty-nine patients were assessable after completing the 35 mg/m2 b.i.d. schedule. The investigator-determined DCR was 65.5% (95% confidence interval [CI], 45.7–82.1%) and the independent central review's DCR was 51.9% (n = 27, 95% CI, 31.9–71.3%). The median PFS and OS were 2.9 months (95% CI, 1.1–5.3 months) and 8.7 months (95% CI, 5.7–14.9 months), respectively. The grade 3/4 adverse events included neutropenia (69.0%), leukopenia (41.4%), anemia (20.7%), and anorexia (10.3%). No AGC-specific toxicities were detected. In the expanded cohort, the averages of PK parameters dose-dependently increased for 6 patients treated with the 40 mg/m2 b.i.d. dosage. Although slightly higher grade 3–4 neutropenia (83.3%) and leukopenia (66.7%) were observed, the investigator-determined DCR was 50.0% (SD: 3; PD: 3) and no partial response cases were observed.

Conclusions

The 35 mg/m2 b.i.d. dose of TAS-102 provided positive efficacy and an acceptable toxicity profile in patients with AGC. A randomized, double-blind, placebo-controlled, phase III study is ongoing to validate these findings.

Clinical trial identification

UMIN000007421

Legal entity responsible for the study

Exploratory Oncology Research & Clinical Trial Center, National Cancer Center

Funding

The Renovation Project of Early and Exploratory Clinical Trial Center, National Cancer Center Research and Development Fund (24-A-1)

Disclosure

K. Muro, T. Nishina, A. Ohtsu: Honoraria: Taiho Pharmaceutical Company. S. Takahashi: Research funding: Taiho Pharmaceutical Company. S. Nomura: Japan Breast Cancer Research Group (JBCRG). Grants: Japan Agency for Medical Research and Development (AMED). A. Sato: Corporate-sponsored Research: Taiho, Boehringer-Ingelheim, Novartis, Bayer. All other authors have declared no conflicts of interest.