159397-173

TAS-102 versus placebo plus best supportive care in patients with metastatic colorectal cancer refractory to standard therapies: Final survival results of the phase III RECOURSE trial.

Category: 
Cancers of the Colon, Rectum, and Anus
Session Type and Session Title: 
Poster Session C: Cancers of the Colon, Rectum, and Anus
Abstract Number: 

634

Poster Board Number: 
Poster Session C Board #G17
Citation: 
J Clin Oncol 34, 2016 (suppl 4S; abstr 634)
Author(s): 
Robert J. Mayer, Atsushi Ohtsu, Takayuki Yoshino, Alfredo Falcone, Rocio Garcia-Carbonero, Josep Tabernero, Alberto F. Sobrero, Marc Peeters, Fabio Benedetti, Lukas Makris, Hiroshi Ambe, Alberto Zaniboni, Yasuhiro Shimada, Kentaro Yamazaki, Yoshito Komatsu, Howard S. Hochster, Heinz-Josef Lenz, Ben Tran, Eric Van Cutsem, on behalf of the RECOURSE Study Group; Dana-Farber Cancer Institute, Boston, MA; Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Japan; National Cancer Center Hospital East, Kashiwa, Japan; Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Hospital Universitario Virgen del Rocio, Sevilla, Spain; Vall d’Hebron University Hospital, Barcelona, Spain; IRCCS A.O.U. San Martino IST, Genoa, Italy; Antwerp University Hospital, Edegem, Belgium; Taiho Oncology, Inc., Princeton, NJ; Stathmi, Inc., New Hope, PA; Taiho Pharmaceutical Co., LTD., Tokyo, Japan; Fondazione Poliambulanza, Brescia, Italy; National Cancer Center Hospital, Chuo-Ku, Japan; Shizuoka Cancer Center, Shizuoka, Japan; Hokkaido University Hospital, Sapporo, Japan; Yale Cancer Center, New Haven, CT; USC Norris Comprehensive Cancer Center, Los Angeles, CA; The Royal Melbourne Hospital, Victoria, Australia; University Hospitals Leuven, Leuven, Belgium

Abstract Disclosures

Abstract: 

Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer refractory/intolerant to standard therapies were evaluated in the RECOURSE trial. Original results of RECOURSE based on the cut-off date of January 24, 2014, in which 72% of mortality events had occurred, demonstrated a significant improvement in overall survival (OS) with TAS-102 vs placebo. Here we report results of an updated survival analysis from RECOURSE and a retrospective analysis of OS outcomes based on a clinical prognostic risk index. Methods: Patients were randomized 2:1 to receive TAS-102 or placebo. Study treatment continued until disease progression, death, or unacceptable toxicity. The primary endpoint was OS; final survival data were collected on October 8, 2014. A clinical OS prognostic risk score was assessed to evaluate OS effect in patients from low to high prognostic score. Prognostic factors contributing to the risk index were from those prespecified in the multivariate modeling assessment of OS outcome. Results: At data cut-off for the final survival analysis, 89% of the 800 patients randomly assigned to TAS-102 or placebo had died, accounting for 138 events in addition to 574 (72%) events included in the original analysis. The updated results for OS are shown in the Table. Conclusions: An updated survival analysis confirmed that OS benefit with TAS-102 was maintained and increased to a full 2 months; improvement in 1-year survival surpassed 10% in these heavily pretreated patients. OS benefit appears to be maintained for all patients in the trial regardless of prognostic status at trial entry. Clinical trial information: NCT01607957

Original Analysis
Updated Analysis
TAS-102
(n=534)
Placebo
(n=266)
TAS-102
(n=534)
Placebo
(n=266)
Median OS, mo
(95% CI)
7.1
(6.5-7.8)
5.3
(4.6-6.0)
7.2
(6.6-7.8)
5.2
(4.6-5.9)
Hazard ratio
(95% CI)
0.68
(0.58-0.81)
0.69
(0.59-0.81)
P value (1-sided)<0.0001<0.0001
1-year survival, %
(95% CI)
26.6
(22.2-31.1)
17.6
(12.7-23.1)
27.1
(23.3-30.9)
16.6
(12.4-21.4)