Mechanism and effect of trifluridine and tipiracil (Lancever) in the treatment of colon cancer

Since2015, trifluridine and tipiracil (Lonsurf) have become a new treatment modality for patients with advanced colorectal cancer who have failed to respond to various other therapies. In August 2023, the combination therapy of this drug and bevacizumab opened up a new treatment avenue for adult patients with metastatic colorectal cancer (mCRC) who had failed previous treatments.

Trifluridine and tipiracil are unique in their role as inhibitors of nucleoside metabolism, able to fit neatly intoDNA structure and disrupt its normal function. Tipiracil, as an enzyme inhibitor, helps maintain a stable level of trifluridine in the blood, thereby enhancing the therapeutic effect.

In a colorectal cancer study of trifluridine and tipiracil alone, the results were encouraging. Compared with patients who received placebo, whose median survival was 5.3 months, patients who received trifluridine and tipiracil lived on average 7.1 months. Specifically, survival for patients in the trifluridine-tipiracil treatment group ranged from 6.5 months to 7.8 months. In addition, the average time to cancer progression in patients treated with trifluridine and tipiracil was 2 months, and 88% of patients experienced disease progression or death, a data that reflects the drug's positive effect in delaying disease progression.

In the pivotal Phase 3 clinical trialSUNLIGHT, the combination therapy of trifluridine tipiracil and bevacizumab showed amazing results. For patients with metastatic colorectal cancer, the average survival time in the combination group reached 10.8 months, compared with only 7.5 months in patients who received trifluridine and tipiracil alone. This means the combination therapy reduced patients' risk of death by a full 39%. Meanwhile, in terms of progression-free survival (PFS), patients who received the combination therapy had an average of 5.6 months, compared with only 2.4 months for those who received only trifluridine and tipiracil. This result reduces the relative risk of disease progression by up to 56%, providing a new option for patients in treatment dilemma.