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


Key Points

  • TAS-102 prolonged overall survival by 1.8 months compared to placebo in patients with metastatic colorectal cancer refractory to standard therapy.
  • TAS-102 also improved progression-free survival compared to placebo.
  • The drug was well tolerated, and side effects were mild.

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 (Abstract O-0022).

“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 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.”

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 cancer DNA, leading to DNA dysfunction. However, when trifluridine is taken orally it is largely degraded to an inactive form. Tipiracil hydrochloride has angiogenic activity and 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.


The current RECOURSE study 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, bevacizumab (Avastin), and cetuximab (Erbitux), or panitumumab (Vectibix) for patients with 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 (34.9%), leukopenia (12.8%), and anemia (16.5%). Febrile neutropenia was observed in 3.8% of patients receiving TAS-102.

New Treatment Option

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

Commenting on the data, ESMO spokesperson Jean-Yves Douillard, MD, PhD, Professor of Medical Oncology, Institut de Cancérologie de l’Ouest (ICO) René Gauducheau, Saint-Herblain, France, said, “The phase III trial of TAS-102 is a global study and confirms the results of the phase II study in Japanese patients, whose response to fluoropyrimidine is slightly different to patients in Europe and the United States. It is good to know that the magnitude of benefit shown in the smaller phase II trial is confirmed in the larger phase III trial and that the results apply to Asians and Caucasians alike.”

Dr. Douillard concluded, “In RECOURSE, TAS-102 was tested in patients who had received all types of chemotherapy available for colorectal cancer. I would probably move this drug into an earlier line of treatment and I would also combine it with either irinotecan or oxaliplatin.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.