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
1049 - The Effect Of Multiple Interventions For Women At Risk For Cervical Cancer On Their Health Responsibility, Beliefs Regarding Cervical Cancer, And Having Screening: A Randomized Controlled Experiment
Presenter: Busra Altinel
Session: Poster Display session 2
Resources:
Abstract
1309 - Quantifying the Effects of the Korean National Cancer Screening Program on Cervical Cancer Mortality
Presenter: Nhung Bui
Session: Poster Display session 2
Resources:
Abstract
1346 - Spread of tumor and adverse events after modified radical hysterectomy for FIGO Stage IB1 cervical cancer patients with tumor diameter preoperatively estimated 2 cm or less: Japan Clinical Oncology Group trial (JCOG1101); exploratory analysis before primary analysis.
Presenter: Takahide Arimoto
Session: Poster Display session 2
Resources:
Abstract
5352 - Impact of Combined Interstitial and Intracavitary Brachytherapy in locally advanced Cervical cancer: A Survival and toxicity profile assessment
Presenter: Vibhay Pareek
Session: Poster Display session 2
Resources:
Abstract
2049 - Chemoradiotherapy response prediction model by proteomic expressional profiling in patients with locally advanced cervical cancer
Presenter: Chel Hun Choi
Session: Poster Display session 2
Resources:
Abstract
1923 - Disparities starting adjuvant chemotherapy for locally advanced cervix cancer in the international, academic, randomised, phase 3 OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274)
Presenter: Linda Mileshkin
Session: Poster Display session 2
Resources:
Abstract
3284 - Primary results from CECILIA, a global single-arm phase 2 study evaluating bevacizumab (BEV), carboplatin (C) and paclitaxel (P) for advanced cervical cancer (aCC)
Presenter: Andres Redondo
Session: Poster Display session 2
Resources:
Abstract
843 - Prognostic and clinicopathological significance of PD-L1 in patients with cervical cancer: a meta-analysis
Presenter: Xiaobin Gu
Session: Poster Display session 2
Resources:
Abstract
1020 - Clinical impact of molecular profiling of cervical cancer (CC) patients (pts) in a dedicated Phase I (P1) unit
Presenter: Mariana Scaranti
Session: Poster Display session 2
Resources:
Abstract
872 - Comparative proteomic profiles of cervical cancer and paried paracancerous tissue and the potential effects of DUSP7 over-expression through inhibiting RAS pathway on the biological characteristics of human cervical cancer cell line SIHA
Presenter: Xuan Jiang
Session: Poster Display session 2
Resources:
Abstract