Lonsurf (trifluridine and tipiracil)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved September 2015

Specific Treatments:

metastatic colorectal cancer and metastatic gastric or gastroesophageal junction adenocarcinoma

Therapeutic Areas

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General Information

Lonsurf is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor.

Lonsurf is specifically indicated for the following:

• patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. 

• patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

Lonsurf is supplied as tablet for oral administration. The recommended dose is 35 mg/m2 /dose orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. Lonsurf should be administered within 1 hour after completion of morning and evening meals. 

Clinical Results

FDA Approval

The FDA approval of Lonsurf for colorectal cancer was based on an international, randomized, double-blind, placebo-controlled study conducted in patients with previously treated metastatic colorectal cancer. A total of 800 patients were randomized 2:1 to receive Lonsurf (N=534) plus best supportive care (BSC) or matching placebo (N=266) plus BSC. Randomization was stratified by KRAS status (wild-type vs. mutant), time since diagnosis of first metastasis (<18 months vs. ≥ 18 months), and region (Japan vs. US, Europe and Australia). Patients received 35 mg/m2 Lonsurf or matching placebo orally twice daily after meals on Days 1 - 5 and 8 – 12 of each 28-day cycle until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall survival (OS) and an additional efficacy outcome measure was progression-free survival (PFS). A statistically significant improvement in overall survival and progression-free survival were demonstrated in patients in the Lonsurf plus BSC arm compared to those who received placebo plus BSC. Median OS (months) was 7.1 versus 5.3. PFS was 88% versus 94%, respectively.

The FDA approval of Lonsurf for gastric cancer was based on the phase III trial, TAGS (TAS-102 Gastric Study). The global, randomized, double-blind study evaluated Lonsurf (35 mg/m2 orally twice daily on Days 1-5 and 8-12 of each 28-day cycle) plus best supportive care (BSC) versus placebo plus BSC in 507 patients with metastatic gastric or GEJ cancer, refractory to standard treatments. The primary endpoint in the TAGS trial was Overall Survival (OS). Median overall survival was 5·7 months in the trifluridine/tipiracil group and 3·6 months in the placebo group.

Side Effects

Adverse effects associated with the use of Lonsurf may include, but are not limited to, the following:

  • anemia
  • neutropenia
  • asthenia/fatigue
  • nausea
  • thrombocytopenia
  • decreased appetite
  • diarrhea
  • vomiting
  • abdominal pain
  • pyrexia

Mechanism of Action

Lonsurf  is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor. Following uptake into cancer cells, trifluridine is incorporated into DNA, interferes with DNA synthesis and inhibits cell proliferation. 

Additional Information

For additional information regarding Lonsurf or colorectal cancer/metastatic gastric or gastroesophageal junction adenocarcinoma, please visit https://www.lonsurf.com/