On September 22, 2015, the U. S. Food and Drug Administration approved trifluridine/tipiracil (LONSURF, Taiho Oncology, Inc.) for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- , and irinotecan-based chemotherapy, an anti-VEGF biologic product, and an anti-EGFR monoclonal antibody, if RAS wild-type.
The approval was based on the demonstration of improved overall survival (OS) in a multicenter, double-blind, placebo-controlled trial (TPU-TAS-102-301). A total of 800 patients with previously treated metastatic colorectal cancer were randomly allocated (2:1) to receive trifluridine/tipiracil (N=534) plus best supportive care (BSC) or matching placebo (N=266) plus BSC. Key eligibility criteria included ECOG 0-1, absence of brain metastasis, and absence of ascites requiring drainage in the past four weeks. Patients received 35 mg/m2 trifluridine/tipiracil (based on trifluridine component) or matching placebo orally twice daily on days 1 - 5 and 8 – 12 of each 28-day cycle until disease progression or unacceptable toxicity.
A statistically significant improvement in OS was demonstrated [HR 0.68 (95% CI: 0.58, 0.81), p<0.001, stratified log-rank test]; the median OS was 7.1 and 5.3 months in the trifluridine/tipiracil and placebo arms, respectively. PFS was also improved in patients randomly allocated to receive trifluridine/tipiracil [HR 0.47 (95% CI: 0.40, 0.55), p<0.001, stratified log-rank test].
The most common adverse drug reactions or laboratory abnormalities were anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, and pyrexia. The most common adverse reactions leading to dose reduction were neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea.
The recommended dose and schedule for trifluridine/tipiracil is 35 mg/m2 (based on trifluridine component) orally twice daily within one hour of completion of morning and evening meals on days 1 through 5 and days 8 through 12 of each 28-day cycle until disease progression or unacceptable toxicity.
Full prescribing information is available at:
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).