MADRID – Treatment with a new nucleoside-analogue drug produced clinically meaningful improvements in survival and performance status in a phase III trial that enrolled 800 patients with metastatic colorectal cancer who had failed at least two prior chemotherapy regimens.
In addition to a statistically significant, 32% cut in mortality during a median follow-up of 8 months, treatment with TAS-102 was “well tolerated,” and extended the time to deterioration of performance status by more than 40% compared with patients randomized to placebo, Dr. Erik Van Cutsem said at the European Society for Medical Oncology Congress.
Mitchel L. Zoler/Frontline Medical News
Dr. Eric Van Cutsem
S-102’s ability to stabilize patient performance status, along with its benefit for the study’s primary endpoint of overall survival, is “an important clinical parameter, a real benefit” that shows the drug’s positive effect on quality of life, said Dr. Cutsem, professor and head of clinical digestive oncology at the University Hospital, Leuven, Belgium.
TAS-102 contains trifluridine, a nucleoside analogue that gets incorporated into tumor cell DNA, causing dysfunction and inhibited tumor growth. A second agent in the TAS-120 formulation, tipiracil hydrochloride, inhibits trifluridine breakdown.
The RECOURSE (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) trial randomized 800 patients with metastatic colorectal cancer who had failed at least two prior regimens at 114 sites in 13 countries from June 2012 to October 2013. More than half the patients had failed or were intolerant of at least four prior regimens, and more than three-quarters of enrolled patients had been diagnosed with metastatic disease 18 months prior to study entry. Patients’ median age was 63 years, and at entry they all had an Eastern Cooperative Oncology Group performance status rating of 0 or 1.
Patients received 35 mg/m2 oral TAS-102 b.i.d. on days 1-5 and 8-12 for one cycle, repeated every 4 weeks, or placebo in addition to best supportive care. Treatment with the active agent produced a hazard ratio of 0.68 (confidence interval, 0.58-0.81; P < .0001), Dr. Van Cutsem reported. After 1 year, 27% of the 534 patients on TAS-102 treatment remained alive, compared with 18% of the 266 patients randomized to placebo. Prespecified subgroup analyses showed a consistent benefit across all subgroups.
A multivariate analysis showed a similar impact of treatment on overall survival. Secondary analysis showed that TAS-102 treatment was linked to a significant improvement in progression-free survival (HR, 0.48; CI, 0.41-0.57; P < .0001). The median time to deterioration to a performance status rating of 2 was 5.7 months among patients who received TAS-102 and 4.0 months among placebo patients.
TAS-102 produced a low level of nonhematologic grade 3 or 4 adverse events. The most common, usually grade 1 or 2, were nausea, fatigue, diarrhea, and vomiting. It did not produce any excess cardiac or thromboembolic events, and had no effect on liver function or creatinine levels. The novel agent produced a 38% incidence of grade 3 or 4 neutropenia, but grade 3 or 4 febrile neutropenia was limited to 4% of patients, Dr. Van Cutsem noted. Grade 3 anemia occurred in 18% of patients on the combination agent, and 5% had grade 3 or 4 thrombocytopenia.
RECOURSE was sponsored by Taiho, which is developing TAS-102. Dr. Van Cutsem has received research funding from Amgen, Bayer, Boehringer, Lilly, Merck Serono, Novartis, Roche, and Sanofi.
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