Abstract
SummaryIntroduction 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.
Highlights
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer incidence and cancer-related mortality worldwide [1]
Despite recent advances, most patients still progress after treatment, and cytotoxic chemotherapies remain essential in NSCLC treatment algorithms [3, 4]
Baseline characteristics were generally balanced in the two groups, except for sex, Eastern Cooperative Oncology Group performance status (ECOG PS), and epidermal growth factor receptor (EGFR) mutation status (Table 1)
Summary
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer incidence and cancer-related mortality worldwide [1]. The development of immunotherapy and its combination with cytotoxic chemotherapies has garnered new options for therapeutics in advanced NSCLC [2]. Despite recent advances, most patients still progress after treatment, and cytotoxic chemotherapies remain essential in NSCLC treatment algorithms [3, 4]. Highly efficacious, well-tolerated chemotherapies are still warranted. S-1 is an oral 5-fluorouracil (5-FU) derivative that is widely used for the treatment of various solid tumors, including NSCLC [5]. A phase 3 study of S-1 monotherapy demonstrated non-inferiority compared with docetaxel in patients with NSCLC; S-1 is considered a standard chemotherapy option in East Asia [6]
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