Trifluridin / Tipiracil (3) – Lonsurf®

• Clinical trials
  • The RECOURSE trial is an international, randomised, double-blind Phase III trial in which trifluridine/tipiracil was directly compared with placebo, and best standard care (BSC) formed part of the treatment in both treatment groups.
  • The TERRA trial is a double-blind RCT conducted in Asia to compare trifluridine/tipiracil + BSC with placebo + BSC.

Adult patients with metastatic colorectal cancer (CRC) who have already been treated with available therapies or who are unsuitable for these. These therapies include fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, as well as anti-VEGF and anti-EGFR agents.

• For adult patients with metastatic colorectal cancer (CRC) who have already been treated with available therapies, including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF and anti-EGFR agents, or who are not suitable for these, there is a hint of a minor additional benefit.
• Although a meta-analysis of two studies is available, for these reasons the certainty of the evidence (probability of additional benefit) for the overall conclusion on additional benefit is classified as a hint.
• mortality
  • The meta-analysis of the RECOURSE and TERRA studies shows a statistically significant prolongation of overall survival with treatment using trifluridine/tipiracil + BSC compared with BSC.
  • Taking into account the advanced stage of the disease and treatment, the extension in survival time achieved is assessed as a relevant improvement, though one that does not go beyond a minor extent.
• morbidity
  • Symptoms were not assessed in the RECOURSE and TERRA studies.
  • The meta-analysis shows a statistically significant prolongation of PFS for treatment with trifluridine/tipiracil + BSC compared with BSC.
  • The PFS endpoint is a composite endpoint comprising endpoints from the categories of mortality and morbidity.
  • Morbidity was assessed not primarily on the basis of disease symptoms, but solely on the basis of asymptomatic findings not directly relevant to the patient.
• Health-related quality of life
  • Health-related quality of life was not assessed in the RECOURSE and TERRA studies.
  • The data on health-related quality of life from the TALLISUR study are highly limited in their interpretability and cannot be used for the benefit assessment.
• Side effects
  • Adverse events (with and without progression of the underlying disease) occurred at least once in almost all patients in the RECOURSE and TERRA studies; consequently, no conclusions regarding the assessment of additional benefit can be drawn from a comparison of the two study arms.
  • However, in the analysis of AEs excluding events attributable to progression of the underlying disease, the RECOURSE study showed no statistically significant difference between the treatment arms.
  • For the endpoint of discontinuation due to AEs, the meta-analysis shows a statistically significant advantage for treatment with trifluridine/tipiracil compared with BSC.
  • In detail, there is a statistically significant disadvantage for trifluridine/tipiracil in terms of the specific AEs for the endpoint of myelosuppression (CTCAE grade ≥ 3), with the common manifestations of anaemia, febrile neutropenia, leukopenia and neutropenia; as well as a statistically significant disadvantage for trifluridine/tipiracil for the endpoint of gastrointestinal toxicity (SOC: gastrointestinal disorders), with the common manifestations of diarrhoea, nausea and vomiting.
• Overall assessment
  • With regard to overall survival, treatment with trifluridine/tipiracil resulted in a prolongation of survival time compared with best supportive care; this is assessed as a relevant improvement, albeit one that does not go beyond a minor extent.
  • Symptoms and health-related quality of life were not assessed in the RECOURSE and TERRA studies.
  • An overall review of the results regarding side effects reveals neither an advantage nor a disadvantage.
  • In the overall assessment, a moderate – rather than merely minor – improvement in treatment-related benefit is identified, and thus a minor additional benefit of trifluridine/tipiracil compared with best supportive care is identified.

Courtesy translation only, please refer to the German original.