TAS-102 Effective for Wild-Type, Mutant KRAS mCRC

A subgroup analysis of the phase III RECOURSE trial has shown that TAS-102, a combination of an antineoplastic thymidine-based nucleoside analog, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride, is effective at improving survival in patients with both KRAS wild-type or mutant metastatic colorectal cancer.

Results of the subgroup analysis (abstract O-0010) were presented by Howard S. Hochster, MD, of Yale Cancer Center, at the ESMO World Congress on Gastrointestinal Cancer 2015 in Barcelona.

The trial included patients with metastatic disease refractory/intolerant to standard therapies. Patients had to have had two or more prior lines of standard chemotherapy to be included. Previously reported results of the primary analysis showed that TAS-102 significantly improved both overall survival (HR = 0.68; P < .0001) and progression-free survival (HR = 0.48; P < .0001) compared with placebo.

In this subgroup analysis, Hochster and colleagues evaluated the efficacy of TAS-102 in patients who had tumors that were KRAS wild-type or mutant. Of the initial study population, 49.3% of patients had wild-type tumors and 50.8% had KRAS mutant tumors.

Wild-type patients treated with TAS-102 had significant improvement in both overall survival (8 vs 5.7 months; P < .0001) and progression-free survival (2.1 vs 1.7 months; P < .0001). Patients with mutant tumors had significant improvements in progression-free survival vs placebo (1.9 months vs 1.8 months; P < .001), but not in overall survival (6.5 months vs 4.9 months; P = .0712).

The researchers noted that the small number of patients in the study with BRAF status identified precluded any meaningful analysis.

No differences in the incidence of adverse events, grade 3 or worse adverse events, or serious adverse events were noted based on KRAS mutation status.

Commenting on the data in a press release, Dr. Dirk Arnold, ESMO spokesperson, director of the Department of Medical Oncology, Klinik für Tumorbiologie in Freiburg, Germany, said: “Overall there were no large differences in efficacy or in the incidence of adverse events according to KRAS status. However, patients with wild type status had a better outcome than those with mutant status. That underlines our knowledge that the mutation confers a poorer prognosis, now also proven in largely pre-treated patients, and not that TAS-102 is less effective in these patients.”

He added: “There were no differences in adverse events between mutant and wild type groups. This is also not surprising because as far as we know the mechanism of action of TAS-102 is not correlated to KRAS or BRAF mutational status.”