Phase III Trial Shows Improved Survival With TAS‑102 in Metastatic Colorectal Cancer Refractory to Standard Therapies


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The RECOURSE study shows that TAS-102 improves overall survival in these patients compared to placebo. I believe that this agent will become one of the standards of care in the refractory setting of metastatic colorectal cancer in Japan and worldwide.

—Takayuki Yoshino, MD


The new combination agent TAS-102 can improve overall survival compared to placebo in patients whose metastatic colorectal cancer is refractory to standard therapies, researchers reported at the ESMO 16th World Congress on Gastrointestinal Cancer in Barcelona.1

“Around 50% of patients with colorectal cancer develop metastases, but eventually many of them do not respond to standard therapies,” said Takayuki Yoshino, MD, of the National Cancer Centre Hospital East in Chiba, Japan, lead author of the phase III ­RECOURSE trial. “The RECOURSE trial shows that TAS-102 improves overall survival in these patients compared to placebo. I believe that this agent will become one of the standards of care in the refractory setting of metastatic colorectal cancer in Japan and worldwide.”

TAS-102 is a novel nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride. Trifluridine is the active component of TAS-102 and is directly incorporated into DNA, leading to DNA dysfunction. However, when trifluridine is taken orally it is largely degraded to an inactive form. Tipiracil hydrochloride prevents the degradation of trifluridine. This mechanism of action is different from that of a fluoropyrimidine, oxaliplatin, and ­irinotecan.

The phase II trial of TAS-102 had found an overall survival benefit in Japanese patients with metastatic colorectal cancer refractory to the fluoropyrimidine fluorouracil (5-FU), irinotecan, and oxaliplatin.2

RECOURSE Trial

The current RECOURSE trial was a global phase III trial conducted in 13 countries at 114 centers. Patients had metastatic colorectal cancer refractory to all standard therapies including fluoropyrimidines, oxaliplatin, irinotecan, and bevacizumab (Avastin); and cetuximab (Erbitux), or panitumumab (Vectibix) for patients who had wild-type KRAS tumors. Patients were randomly assigned 2:1 to TAS-102 (n = 534) or placebo (n = 266). The primary endpoint was overall survival.

The researchers found that TAS-102 prolonged overall survival compared to placebo (hazard ratio [HR] = 0.68); median overall survival was 7.1 months for TAS-102 and 5.3 months for placebo. TAS-102 also improved progression-free survival compared to placebo (HR = 0.48), which was a secondary endpoint. Dr. Yoshino said, “We found a statistically significant difference in overall and progression-free survival, and a clinically meaningful improvement.”

TAS-102 had a mild safety profile. The most common grade > 3 adverse events were neutropenia (37.9%), leukopenia (21.4%), and anemia (18.2%). Febrile neutropenia was observed in 3.8% of patients receiving TAS-102.

“Patients with metastatic colorectal cancer refractory to standard therapies now have a strong treatment option,” Dr. Yoshino said. ■

Disclosure: Dr. Yoshino reported no potential conflicts of interest.

References

1. Yoshino T, Mayer R, Falcone A, et al: Results of a multicenter, randomized, double-blind, phase III study of TAS-102 vs placebo, with best supportive care in patients with metastatic colorectal cancer refractory to standard therapies. Ann Oncol 25(suppl 2):114, 2014.

2. Yoshino T, Mizunuma N, Yamazaki K, et al: TAS-102 monotherapy for pretreated metastatic colorectal cancer: A double-blind, randomized, placebo-controlled phase II trial. Lancet Oncol 13(10):993-1001, 2012.



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