Abstract 3000
Background
High deoxyuridine triphosphatase (dUTPase) in tumor tissue, as a gatekeeper enzyme for 5-fluorouracil (5-FU), is associated with 5-FU resistance. TAS-114 is an oral dUTPase inhibitor which enhance antitumor activity with 5-FU or fluoropyrimidines. Phase I study of TAS-114 in combination with S-1 showed its tolerability and preliminary antitumor signals for patients (pts) with non-small cell lung cancer and advanced gastric cancer (AGC). This phase II study has been conducted to evaluate efficacy and safety of TAS-114 and S-1 combination in pts with AGC.
Methods
The main eligibility criteria is pts with AGC after two or more previous chemotherapy regimens containing fluoropyrimidines, platinum agents, and taxanes or irinotecan. The primary endpoint is objective response rate (ORR) by investigators’ judgement. Using Simon’s optimal two-stage design, 29 pts were required, with one-sided a = 5% and power=80%. The threshold and expected ORRs were 5% and 25%. Protein expression levels of dUTPase and BRCA1 in tumor samples were determined by immunohistochemistry.
Results
The accrual was terminated in June 2018. Of all 20 enrolled pts, the ORR and disease control rate were 5.0% (95% confidence interval [CI], 0.1-24.9%) and 70.0% (95% CI, 45.7-88.1%), respectively. The median progression-free survival (PFS) and overall survival were 2.4 months (95% CI, 1.2-3.3 months) and 7.1 months (95% CI, 5.2-9.4 months), respectively. The median PFS in the groups with high and low dUTPase protein expression in the cytoplasm was 2.8 months (95% CI, 1.4–3.9) and 1.6 months (95% CI, 0.6–2.4), respectively (hazard ratio, 0.40 [95% CI, 0.16–1.04], P = 0.047). Grade 3 or higher treatment-related adverse events were anemia (20%), leucopenia (15%), neutropenia (10%), rash (10%), thrombocytopenia (5%), and Iymphopenia (5%).
Conclusions
TAS-114 with S-1 showed modest antitumor activity with acceptable safety profiles for heavily pretreated pts with AGC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Taiho.
Disclosure
D. Takahari: Research grant / Funding (self): Taiho Pharmaceutical Co; Research grant / Funding (self): Ono Pharmaceutical Co; Honoraria (self): Eli Lilly Japan; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Yakult Honsha Co; Honoraria (self): Chugai Pharmaceutical Co., Ltd. A. Kawazoe: Honoraria (self), Research grant / Funding (institution): Taiho. K. Shitara: Honoraria (self): Novartis; Honoraria (self): AbbVie; Honoraria (self): Yakult; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Ono Pharmaceutical; Advisory / Consultancy: MSD; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (self): Lilly; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Medi Science. All other authors have declared no conflicts of interest.
Resources from the same session
5205 - Immune status of patients with different stages of colorectal cancer with and without circulating tumor cells
Presenter: Anastasia Sitkovskaya
Session: Poster Display session 2
Resources:
Abstract
5658 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Early Diagnosis of Colorectal Cancer
Presenter: Tianyu Liu
Session: Poster Display session 2
Resources:
Abstract
5779 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Prediction of The Efficacy of Conversion Therapy for Colorectal Cancer Liver Metastases
Presenter: Wenju Chang
Session: Poster Display session 2
Resources:
Abstract
4672 - mCRC gene profiling using the Idylla platform
Presenter: Christopher Bricogne
Session: Poster Display session 2
Resources:
Abstract
3393 - PIK3CA mutation in metastatic colorectal cancer (mCRC): association with clinico-pathological features and outcome
Presenter: Valentina Fanotto
Session: Poster Display session 2
Resources:
Abstract
1317 - Patient-Derived Xenografts (PDX) Identifies JMJD6 Inhibitor as an Effective Therapeutic Medicine in Colorectal Cancer.
Presenter: Feng Ye
Session: Poster Display session 2
Resources:
Abstract
1228 - DACH1 induced stemness of intestinal organoids by directly suppressing BMP signaling and contributes to intestinal tumorigenesis
Presenter: Xiang Hu
Session: Poster Display session 2
Resources:
Abstract
1147 - miR-148a inhibits early relapsed colorectal cancers and the secretion of VEGF by indirectly targeting HIF-1α under non-hypoxia/hypoxia conditions
Presenter: Hsiang-lin Tsai
Session: Poster Display session 2
Resources:
Abstract
1158 - Long noncoding RNA CASC21 promotes cell proliferation and metastasis in colon cancer.
Presenter: Qun Zhang
Session: Poster Display session 2
Resources:
Abstract
1259 - Prognostic and Predictive Impact On FMS-like Tyrosine Kinase 3 (FLT3) Amplification In Patients With Metastatic Colorectal Cancer
Presenter: Hiroko Hasegawa
Session: Poster Display session 2
Resources:
Abstract