Randomized trial of TAS-102 for refractory metastatic colorectal cancer.

Abstract

BACKGROUND:

Early clinical trials conducted primarily in Japan have shown that TAS-102, an oral agent that combines trifluridine and tipiracil hydrochloride, was effective in the treatment of refractory colorectal cancer. We conducted a phase 3 trial to further assess the efficacy and safety of TAS-102 in a global population of such patients.

METHODS:

In this double-blind study, we randomly assigned 800 patients, in a 2:1 ratio, to receive TAS-102 or placebo. The primary end point was overall survival.

RESULTS:

The median overall survival improved from 5.3 months with placebo to 7.1 months with TAS-102, and the hazard ratio for death in the TAS-102 group versus the placebo group was 0.68 (95% confidence interval [CI], 0.58 to 0.81; P<0.001). The most frequently observed clinically significant adverse events associated with TAS-102 were neutropenia, which occurred in 38% of those treated, and leukopenia, which occurred in 21%; 4% of the patients who received TAS-102 had febrile neutropenia, and one death related to TAS-102 was reported. The median time to worsening performance status (a change in Eastern Cooperative Oncology Group performance status [on a scale of 0 to 5, with 0 indicating no symptoms and higher numbers indicating increasing degrees of disability] from 0 or 1 to 2 or more) was 5.7 months with TAS-102 versus 4.0 months with placebo (hazard ratio, 0.66; 95% CI, 0.56 to 0.78; P<0.001).

CONCLUSIONS:

In patients with refractory colorectal cancer, TAS-102, as compared with placebo, was associated with a significant improvement in overall survival. (Funded by Taiho Oncology-Taiho Pharmaceutical; RECOURSE ClinicalTrials.gov number, NCT01607957.).

• Authors: Robert J Mayer, Eric Van Cutsem, Alfredo Falcone, Takayuki Yoshino, Rocio Garcia-Carbonero, Nobuyuki Mizunuma, Kentaro Yamazaki, Yasuhiro Shimada, Josep Tabernero, Yoshito Komatsu, Alberto Sobrero, Eveline Boucher, Marc Peeters, Ben Tran, Heinz-Josef Lenz, Alberto Zaniboni, Howard Hochster, James M Cleary, Hans Prenen, Fabio Benedetti, Hirokazu Mizuguchi, Lukas Makris, Masanobu Ito, Atsushi Ohtsu, RECOURSE Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 372 Issue 20 Pg. 1909-19 (May 14 2015) ISSN: 1533-4406 [Electronic] United States
• PMID: 25970050 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Combinations
• Pyrrolidines
• trifluridine tipiracil drug combination
• Uracil
• Thymine
• Trifluridine

Topics

• Adenocarcinoma (drug therapy, mortality, secondary)
• Adult
• Aged
• Aged, 80 and over
• Colorectal Neoplasms (drug therapy, mortality, pathology)
• Double-Blind Method
• Drug Combinations
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis (drug therapy)
• Proportional Hazards Models
• Pyrrolidines
• Survival Analysis
• Thymine
• Trifluridine (adverse effects, therapeutic use)
• Uracil (adverse effects, analogs & derivatives, therapeutic use)