Randomized trial of TAS-102 for refractory metastatic colorectal cancer

TY - JOUR

T1 - Randomized trial of TAS-102 for refractory metastatic colorectal cancer

AU - Mayer, Robert J

AU - Van Cutsem, Eric

AU - Falcone, Alfredo

AU - Yoshino, Takayuki

AU - Garcia-Carbonero, Rocio

AU - Mizunuma, Nobuyuki

AU - Yamazaki, Kentaro

AU - Shimada, Yasuhiro

AU - Tabernero, Josep

AU - Komatsu, Yoshito

AU - Sobrero, Alberto

AU - Boucher, Eveline

AU - Peeters, Marc

AU - Tran, Ben

AU - Lenz, Heinz-Josef

AU - Zaniboni, Alberto

AU - Hochster, Howard

AU - Cleary, James M

AU - Prenen, Hans

AU - Benedetti, Fabio

AU - Mizuguchi, Hirokazu

AU - Makris, Lukas

AU - Ito, Masanobu

AU - Ohtsu, Atsushi

AU - RECOURSE Study Group

PY - 2015/5/14

Y1 - 2015/5/14

N2 - 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.).

AB - 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.).

KW - Adenocarcinoma/drug therapy

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Colorectal Neoplasms/drug therapy

KW - Double-Blind Method

KW - Drug Combinations

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasm Metastasis/drug therapy

KW - Proportional Hazards Models

KW - Pyrrolidines

KW - Survival Analysis

KW - Trifluridine/adverse effects

KW - Uracil/adverse effects

U2 - 10.1056/NEJMoa1414325

DO - 10.1056/NEJMoa1414325

M3 - SCORING: Journal article

C2 - 25970050

VL - 372

SP - 1909

EP - 1919

JO - NEW ENGL J MED

JF - NEW ENGL J MED

SN - 0028-4793

IS - 20

ER -