What line of therapy is Lonsurf (trifluridine/tipiracil)?

From the Guidelines

Lonsurf (trifluridine/tipiracil) is typically used as a third-line or later therapy for metastatic colorectal cancer. It is prescribed for patients who have already progressed on or are intolerant to standard treatments including fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, anti-VEGF biological therapy, and anti-EGFR therapy (for RAS wild-type tumors) 1. The standard dosing is 35 mg/m² twice daily on days 1-5 and 8-12 of each 28-day cycle, with dose adjustments based on toxicity. Lonsurf works through a dual mechanism: trifluridine incorporates into DNA causing strand breaks, while tipiracil prevents rapid metabolism of trifluridine, increasing its bioavailability. Some key points to consider when using Lonsurf include:

• Common side effects include neutropenia, anemia, fatigue, nausea, and diarrhea, so regular blood count monitoring is essential.
• While Lonsurf provides modest survival benefits (approximately 2 months improvement in overall survival compared to placebo), it represents an important option for heavily pretreated patients with limited alternatives.
• The use of Lonsurf is supported by guidelines such as those from the Chinese Society of Clinical Oncology (CSCO) and the National Comprehensive Cancer Network (NCCN) 1.
• Other treatment options, such as regorafenib and fruquintinib, may also be considered for patients with metastatic colorectal cancer who have progressed on standard therapies 1.
• It is essential to carefully evaluate the patient's performance status, prior therapies, and potential toxicities when selecting a treatment regimen.
• The selection of Lonsurf should be based on individual patient factors, including tumor characteristics, prior treatment history, and overall health status.

From the FDA Drug Label

LONSURF, as a single agent or in combination with bevacizumab, is indicated for the treatment of adult patients with metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. LONSURF is indicated for the treatment of adult 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.

Line of Therapy: Lonsurf is indicated for use in patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, and in patients with metastatic gastric or gastroesophageal junction adenocarcinoma who have been previously treated with at least two prior lines of chemotherapy.

• Metastatic Colorectal Cancer: Third-line therapy or later, as a single agent or in combination with bevacizumab.
• Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: Third-line therapy or later. 2 2 2

From the Research

Line of Therapy for Lonsurf

• Lonsurf (trifluridine/tipiracil) is used as a third-line treatment for metastatic colorectal cancer (mCRC) in patients who are refractory to or are not considered candidates for current standard chemotherapy and biological therapy 3, 4, 5.
• It is approved for the treatment of adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an antivascular endothelial growth factor biological therapy, and, if RAS wild-type, an antiepidermal growth factor receptor therapy 4.
• Lonsurf is also used in patients who have received at least 2 prior lines of standard chemotherapy, including fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and an antiepidermal growth factor receptor antibody in patients with KRAS wild-type tumors 4.

Treatment Regimen

• The recommended dose of Lonsurf is 35 mg/m2 twice a day after meals in a 28-day cycle, comprising 2 weeks of 5 days of treatment and 2 days of rest (days 1-5 and 8-12 every 28 days), followed by 2 weeks of rest 3, 4.
• The treatment regimen is based on the results of the RECOURSE trial, which showed that Lonsurf significantly improved overall survival and progression-free survival compared to placebo in patients with mCRC 3, 4.

Patient Population

• Lonsurf is used in patients with mCRC who have failed or are intolerant to standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy 3, 4, 5.
• It is also used in elderly patients (≥ 65 years) with mCRC, who have a similar safety and tolerability profile to younger patients (< 65 years) 6.