TY - JOUR
T1 - A randomized, phase 2 study of deoxyuridine triphosphatase inhibitor, TAS-114, in combination with S-1 versus S-1 alone in patients with advanced non-small-cell lung cancer
AU - Yamamoto, Nobuyuki
AU - Hayashi, Hidetoshi
AU - Planchard, David
AU - Morán, Teresa
AU - Gregorc, Vanesa
AU - Dowell, Jonathan
AU - Sakai, Hiroshi
AU - Yoh, Kiyotaka
AU - Nishio, Makoto
AU - Cortot, Alexis B.
AU - Benhadji, Karim A.
AU - Soni, Nital
AU - Huang, Jinhong
AU - Makris, Lukas
AU - Cedres, Susana
N1 - Funding Information:
This work was supported by Taiho Oncology, Inc. and Taiho Pharmaceutical Co., Ltd. The funding sources played a role in the study design; collection, analysis, and interpretation of data; writing of the report; and in the decision to submit the article for publication. Acknowledgements
Funding Information:
We thank the patients, their families, the investigators (Online Resource Table S2), and sites that participated in this study. The authors would like to thank Keyra Martinez Dunn, MD and Sarah Bubeck, PhD, of Edanz Medical Writing, for providing medical writing support which was funded by Taiho Pharmaceutical Co., Ltd.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Introduction TAS-114 is a potent inhibitor of deoxyuridine triphosphatase, which is a gatekeeper protein preventing uracil and 5-fluorouracil (5-FU) misincorporation into DNA. TAS-114 has been suggested to enhance the antitumor activity of 5-FU. This randomized, phase 2 study investigated TAS-114 plus S-1 (TAS-114/S-1) vs. S-1 in non-small-cell lung cancer (NSCLC) patients. Methods Patients with advanced NSCLC, previously treated with ≥ 2 regimens, were randomized 1:1 to receive TAS-114 (400 mg)/S-1 (30 mg/m2) or S-1 (30 mg/m2). Progression-free survival (PFS, independent central review) was the primary endpoint. Secondary endpoints included disease control rate (DCR), overall survival (OS), overall response rate (ORR), and safety. Results In total, 127 patients received treatment. Median PFS was 3.65 and 4.17 months in the TAS-114/S-1 and S-1 groups, respectively (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.71–1.88; P = 0.2744). DCR was similar between groups (TAS-114/S-1 80.3%, S-1 75.9%) and median OS was 7.92 and 9.82 months for the TAS-114/S-1 and S-1 groups, respectively (HR 1.31, 95% CI 0.80–2.14; P = 0.1431). The ORR was higher in the TAS-114/S-1 group than the S-1 group (19.7% vs. 10.3%), and more patients with tumor shrinkage were observed in the TAS-114/S-1 group. Incidence rates of anemia, skin toxicities, and Grade ≥ 3 treatment-related adverse events were higher in the TAS-114/S-1 group compared with the monotherapy group. Conclusions Although the TAS-114/S-1 combination improved the response rate, this did not translate into improvements in PFS. Clinical Trial Registration No. NCT02855125 (ClinicalTrials.gov) registered on 4 August 2016.
AB - Introduction TAS-114 is a potent inhibitor of deoxyuridine triphosphatase, which is a gatekeeper protein preventing uracil and 5-fluorouracil (5-FU) misincorporation into DNA. TAS-114 has been suggested to enhance the antitumor activity of 5-FU. This randomized, phase 2 study investigated TAS-114 plus S-1 (TAS-114/S-1) vs. S-1 in non-small-cell lung cancer (NSCLC) patients. Methods Patients with advanced NSCLC, previously treated with ≥ 2 regimens, were randomized 1:1 to receive TAS-114 (400 mg)/S-1 (30 mg/m2) or S-1 (30 mg/m2). Progression-free survival (PFS, independent central review) was the primary endpoint. Secondary endpoints included disease control rate (DCR), overall survival (OS), overall response rate (ORR), and safety. Results In total, 127 patients received treatment. Median PFS was 3.65 and 4.17 months in the TAS-114/S-1 and S-1 groups, respectively (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.71–1.88; P = 0.2744). DCR was similar between groups (TAS-114/S-1 80.3%, S-1 75.9%) and median OS was 7.92 and 9.82 months for the TAS-114/S-1 and S-1 groups, respectively (HR 1.31, 95% CI 0.80–2.14; P = 0.1431). The ORR was higher in the TAS-114/S-1 group than the S-1 group (19.7% vs. 10.3%), and more patients with tumor shrinkage were observed in the TAS-114/S-1 group. Incidence rates of anemia, skin toxicities, and Grade ≥ 3 treatment-related adverse events were higher in the TAS-114/S-1 group compared with the monotherapy group. Conclusions Although the TAS-114/S-1 combination improved the response rate, this did not translate into improvements in PFS. Clinical Trial Registration No. NCT02855125 (ClinicalTrials.gov) registered on 4 August 2016.
KW - 5-fluorouracil
KW - Non-small-cell lung cancer
KW - Progression-free survival
KW - dUTPase
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U2 - 10.1007/s10637-020-00930-5
DO - 10.1007/s10637-020-00930-5
M3 - Article
C2 - 32246224
AN - SCOPUS:85083224046
SN - 0167-6997
VL - 38
SP - 1588
EP - 1597
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 5
ER -