Trifluridine-tipiracil plus bevacizumab in metastatic colorectal cancer

In a new study published on The New England Journal of Medicine, treatment with trifluridine-tipiracil (FTD–TPI) plus bevacizumab resulted in significantly longer overall survival and progression-free survival  and better disease control than treatment with FTD–TPI alone.

FTD-TPI is an orally administered combination of trifluridine, a cytotoxic nucleic acid analogue, and tipiracil, a thymidine phosphorylase inhibitor that prevents enzymatic breakdown of trifluridine. The STARLIGHT study is a phase III trial where a total of 246 patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer were randomly assigned to receive FTD–TPI plus bevacizumab or FTD-TPI alone. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD–TPI group; the median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD–TPI group. The most common adverse events in both groups were neutropenia, nausea, and anemia; no treatment-related deaths were reported. This data confirm that FTD-TPI plus bevacizumab is an effective treatment option for patients with refractory metastatic colorectal cancer, irrespective of mutational status, tumour localization and whether patients have previously been treated with bevacizumab. Patients who have disease progression after receiving treatments such as fluorouracil-based chemotherapy with oxaliplatin and irinotecan, VEGF-based treatment (mainly bevacizumab), and EGFR-targeted treatment in case of RAS wild-type tumours, are considered to have refractory disease; however, many of these patients have a good performance status and may be considered for further treatment. The survival benefits of FTD-TPI plus bevacizumab were observed in all subgroups, including the subgroup of patients with factors indicative of a poor prognosis; benefits were observed irrespective of age, sex, location of primary disease, number of metastatic sites, or RAS mutation status and regardless of whether patients had received previous treatment with bevacizumab, a finding that adds to the body of evidence supporting a role for continued inhibition of angiogenesis beyond progression.