Randomized trial of TAS-102 for refractory metastatic colorectal cancer
Standard
Randomized trial of TAS-102 for refractory metastatic colorectal cancer. / RECOURSE Study Group.
In: NEW ENGL J MED, Vol. 372, No. 20, 14.05.2015, p. 1909-19.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
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 -