TAS-102 (trifluridine/tipiracil; Lonsurf) extended overall survival (OS) in previously treated patients with metastatic gastric cancer, according to findings from the phase III TAGS trial.
Specific findings from the pivotal trial will be presented at an upcoming oncology conference, according to Taiho Oncology, the manufacturer of TAS-102. The company is also submitting the data for publication in a peer-reviewed journal.
“We are delighted by these positive results in the TAGS study, which further underscore the activity of Lonsurf in prolonging survival and as a potential treatment option for patients with metastatic gastric cancer who have failed prior treatments,” Martin J. Birkhofer, MD, senior vice president, chief medical officer, Taiho Oncology, said in a statement.
“This is particularly important given that these patients currently have limited approved standard third-line treatment options available to them after first and second line therapies have failed. We look forward to including these data in an sNDA submission to the U.S. Food and Drug Administration (FDA) for consideration as a third-line treatment option for appropriate patients with metastatic gastric cancer,” added Birkhofer.
The double-blind multinational TAGS trial (NCT02500043) randomized 507 patients with metastatic gastric cancer refractory to standard therapies to best supportive care plus either TAS-102 or placebo. Patients were aged ≥18 years and had been treated with 2 or more prior regimens for advanced disease.
TAS-102 was administered at a 35 mg/m2
twice daily on days 1 to 5 and days 8 to 12 of 28-day cycles. The primary endpoint was OS, with secondary endpoints including progression-free survival (PFS), safety/tolerability, and quality of life.
Results were previously published in the European Journal of Cancer
from the phase II EPOC1201 study that examined TAS-102 in 29 previously treated Japanese patients with advanced gastric cancer.1
Patients on the study had received 1 or 2 prior lines of chemotherapy that included fluoropyrimidine, platinum agents, and taxanes or irinotecan.
Patients received TAS-102 at 35 mg/m2
twice daily. The primary endpoint was a disease control rate (DCR) of ≥50% after 8 weeks of treatment with this dosing schedule.
The DCR was 65.5% (95% CI, 45.7-82.1) per investigator review and 51.9% (95% CI, 31.9-71.3) according to independent review. The median PFS was 2.9 months (95% CI, 1.1-5.3) and the median OS was 8.7 months (95% CI, 5.7-14.9). The most common grade III/IV adverse events included neutropenia (69.0%), leucopenia (41.4%), anemia (20.7%), and anorexia (10.3%).
The FDA approved TAS-102 in September 2015 for the treatment of patients with metastatic colorectal cancer (mCRC) who have previously received fluoropyrimidine-, oxaliplatin- , and irinotecan-based chemotherapy, an anti-VEGF biologic product, and an anti-EGFR monoclonal antibody, if RAS
wild-type. The approval was based on the phase III RECOURSE trial.
In the RECOURSE study, the median OS for patients with mCRC who received TAS-102 was 7.1 months compared with 5.3 months with placebo (HR, 0.68; P
The median PFS in the TAS-102 arm was 2 months versus 1.7 months with placebo (HR, 0.48; P
The 1-year OS rate with TAS-102 was 27% compared with 18% with placebo. This benefit was observed across all subgroups in the trial, including those with KRAS mutations and across all geographic regions. Additionally, patients treated with prior regorafenib (Stivarga) experienced responses to TAS-102.
- Bando H, Doi T, Muro K, et al. A multicenter phase II study of TAS-102 monotherapy in patients with pre-treated advanced gastric cancer (EPOC1201). Eur J Cancer. 2016;62:46-53. doi: 10.1016/j.ejca.2016.04.009.
- Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. NEJM. 2015;372:1909-1919.