Randomized trial of TAS-102 for refractory metastatic colorectal cancer
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, Ben Tran, Timothy Price, Nick Pavlakis, Niall Tebbutt, Guy Van Hazel, Kathrin Strasser-Weippl, Andreas Petzer, Werner Scheithauer, Josef Thaler, Jean Luc Canon, Yves Humblet, Stephanie Laurent, Jean-Luc Van Laethem, Eric Van Cutsem, Hans Prenen, Marc Peeters, Eugen Kubala, Antoine Adenis, Thierry Andre, Denis Smith, Fabienne Portales, Eveline Boucher, Christophe Borg, Andreas Block, Dirk Buschmann, Elke Jager, Markus Moehler, Ingo Schwaner, Ralf-Dieter Hofheinz, Meinolf Karthaus, Gunnar Folprecht, Ray McDermott, David Fennelly, Brian Bird, Alessandro Bertolini, Fortunato Ciardiello, Maria Di Bartolomeo, Alfredo Falcone, Emiliano Tamburini, Alberto Sobrero, Marco Tampellini, Alberto Zaniboni, Salvatore Siena, Yoshito Komatsu, Yasushi Tsuji, Hirofumi Fujii, Toshikazu Moriwaki, Kensei Yamaguchi, Atsushi Ohtsu, Takayuki Yoshino, Tadamichi Denda, Nobuyuki Mizunuma, Yasuo Hamamoto, Yasuhiro Shimada, Norisuke Nakayama, Kentaro Yamazaki, Kei Muro, Masahiro Goto, Naotoshi Sugimoto, Akihito Tsuji, Tetsuji Takayama, Tomohiro Nishina, Taito Esaki, Hideo Baba, Cristina Grávalos, Laura Lema, Fernando Rivera, Maria J Safont, Josep Tabernero, Rocio Garcia-Carbonero, Andres Cervantes, Alberto Carmona, Jose L Manzano, Manuel Benavides, Federico Longo, Antonieta Salud, Per Bystrom, Bengt Glimelius, Stephen Falk, Leslie Samuel, David Cunningham, John Bridgewater, Daniel Swinson, Jerilyn Hart, Philip J Stella, Ari D Baron, Ronald Yanagihara, Heinz-Josef Lenz, James Knost, Robert J Mayer, James M Cleary, Nashat Y Gabrail, Howard Hochster, Ali Khojasteh, Timothy C Kasunic, David Ryan, Omar Kayaleh, Pei-Hua Lu, Brian A DiCarlo, Steven J Hager, Devinder Singh, Jyotsna Fuloria, J Marc Pipas, Patrick J Loehrer, 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, Ben Tran, Timothy Price, Nick Pavlakis, Niall Tebbutt, Guy Van Hazel, Kathrin Strasser-Weippl, Andreas Petzer, Werner Scheithauer, Josef Thaler, Jean Luc Canon, Yves Humblet, Stephanie Laurent, Jean-Luc Van Laethem, Eric Van Cutsem, Hans Prenen, Marc Peeters, Eugen Kubala, Antoine Adenis, Thierry Andre, Denis Smith, Fabienne Portales, Eveline Boucher, Christophe Borg, Andreas Block, Dirk Buschmann, Elke Jager, Markus Moehler, Ingo Schwaner, Ralf-Dieter Hofheinz, Meinolf Karthaus, Gunnar Folprecht, Ray McDermott, David Fennelly, Brian Bird, Alessandro Bertolini, Fortunato Ciardiello, Maria Di Bartolomeo, Alfredo Falcone, Emiliano Tamburini, Alberto Sobrero, Marco Tampellini, Alberto Zaniboni, Salvatore Siena, Yoshito Komatsu, Yasushi Tsuji, Hirofumi Fujii, Toshikazu Moriwaki, Kensei Yamaguchi, Atsushi Ohtsu, Takayuki Yoshino, Tadamichi Denda, Nobuyuki Mizunuma, Yasuo Hamamoto, Yasuhiro Shimada, Norisuke Nakayama, Kentaro Yamazaki, Kei Muro, Masahiro Goto, Naotoshi Sugimoto, Akihito Tsuji, Tetsuji Takayama, Tomohiro Nishina, Taito Esaki, Hideo Baba, Cristina Grávalos, Laura Lema, Fernando Rivera, Maria J Safont, Josep Tabernero, Rocio Garcia-Carbonero, Andres Cervantes, Alberto Carmona, Jose L Manzano, Manuel Benavides, Federico Longo, Antonieta Salud, Per Bystrom, Bengt Glimelius, Stephen Falk, Leslie Samuel, David Cunningham, John Bridgewater, Daniel Swinson, Jerilyn Hart, Philip J Stella, Ari D Baron, Ronald Yanagihara, Heinz-Josef Lenz, James Knost, Robert J Mayer, James M Cleary, Nashat Y Gabrail, Howard Hochster, Ali Khojasteh, Timothy C Kasunic, David Ryan, Omar Kayaleh, Pei-Hua Lu, Brian A DiCarlo, Steven J Hager, Devinder Singh, Jyotsna Fuloria, J Marc Pipas, Patrick J Loehrer
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.).
Source: PubMed