Combination Agent in Asian Patients With Previously Treated Metastatic Colorectal Cancer
In the Asian phase III TERRA trial, trifluridine/tipiracil (Lonsurf) produced a significant improvement in overall survival vs placebo among patients with metastatic colorectal cancer refractory or intolerant of standard chemotherapies with or without exposure to biologic therapies. These findings were reported in the Journal of Clinical Oncology by Xu et al.
Study Details
In the double-blind trial, 406 patients from 30 sites in China, the Republic of Korea, and Thailand who were refractory to or intolerant of at least 2 prior chemotherapy regimens were randomized 2:1 between October 2013 and June 2015 to receive oral trifluridine/tipiracil at 35 mg/m2 per dose twice a day orally for 5 days on and 2 days off for 2 weeks followed by 14 days off per 28-day cycle (n = 271) or placebo (n = 135). Targeted biologic therapy had been received by 55% of the trifluridine/tipiracil group and 49% of the placebo group, and 63% of each group had KRAS wild-type status. The primary endpoint was overall survival in the intent-to-treat population.
Overall Survival
Median follow-up was 13.8 months in the trifluridine/tipiracil group and 13.4 months in the placebo group. Median overall survival was 7.8 months vs 7.1 months (hazard ratio [HR] = 0.79, P = .035). Median progression-free survival was 2.0 months vs 1.8 months (HR = 0.43, P < .001). Subgroup analysis indicated a similar survival benefit of trifluridine/tipiracil among patients with wild-type KRAS (median = 8.6 vs 7.4 months, HR = 0.77, P = .083) and those with mutant KRAS (median = 7.0 vs 6.5 months, HR = 0.83, P = .228; P = .885 for interaction).
Adverse Events
Drug-related grade ≥ 3 adverse events occurred in 46% vs 10% of patients, with the most common in the trifluridine/tipiracil group being neutropenia (33%), leukopenia (21%), and anemia (18%). No febrile neutropenia was reported. Serious adverse events occurred in 23% vs 24% of patients. Adverse events led to treatment discontinuation in 10% of both groups. No treatment-related deaths were observed.
The investigators concluded: “Trifluridine/tipiracil has a statistically significant survival benefit compared with placebo in Asian patients with [metastatic colorectal cancer] refractory to or intolerant of standard chemotherapies, regardless of exposure to biologic therapy. The safety profile is similar to previous reports.”
The study was supported by Taiho Pharmaceutical.
Jin Li, MD, of the Tongji University Affiliated Shanghai East Hospital, is the corresponding author of the Journal of Clinical Oncology article.
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