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

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.