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

نویسندگان

  • 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
چکیده

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.).

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عنوان ژورنال:
  • The New England journal of medicine

دوره 372 20  شماره 

صفحات  -

تاریخ انتشار 2015