Taiho Oncology’s Lonsurf approved in USA

The U. S. Food and Drug Administration approved Taiho Oncology’s Lonsurf 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, announced on September 22, was based on the demonstration of improved overall survival (OS) in a multicenter, double-blind, placebo-controlled trial (TPU-TAS-102-301).

“Patients with metastatic colorectal cancer, whose disease has progressed after treatment with standard therapies, have had limited therapeutic options to treat their disease,” said Eric Benn, Taiho Oncology’s President and Chief Executive Officer.

“Lonsurf helps address this unmet medical need by providing patients with a new therapeutic option that can help extend their overall survival. As the first FDA approval for Taiho Oncology, Lonsurf also represents a major milestone for our company.”

“Metastatic colorectal cancer cells often become resistant to previously effective treatment, underscoring the importance of identifying new therapeutic options for patients with the disease,” said Robert J. Mayer, MD, Faculty Vice President for Academic Affairs at the Dana Farber Cancer Institute, Professor of Medicine atHarvard Medical School, and Principal Investigator of the RECOURSE study.

“In a pivotal clinical trial, Lonsurf demonstrated that it can extend overall survival, providing patients and their oncologists with a novel oral therapy.”

FDA says that 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, FDA said.

Acording to FDA, 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].

Also, 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.