Discussion
tumour
TUMOUR
This is the first phase II/III trial to verify the efficacy of FTD/TPI plus bevacizumab as a second-line treatment for patients with mCRC. FTD/TPI plus bevacizumab did not demonstrate noninferiority to fluoropyrimidine and irinotecan plus bevacizumab in terms of OS.PFS and DCR in the FTD/TPI plus bevacizumab group were similar to those reported in the third- or late-line setting [The study was planned assuming that FOLFIRI plus bevacizumab and S-1 and irinotecan plus bevacizumab had similar efficacy; however, in the post hoc analyses, median OS in the S-1 and irinotecan plus bevacizumab treatment tended to be longer than that in the FOLFIRI plus bevacizumab treatment. Some trials have shown that oral fluoropyrimidine plus irinotecan might be more effective than intravenous 5-FU plus irinotecan or oxaliplatin [Although the results of the STL are based on post hoc analyses, OS was similar between the FTD/TPI plus bevacizumab group and the control group in patients with low tumour burden (STL <60 mm). The baseline characteristics in patients with both high and low tumour burden were balanced between the treatment groups. The SOLSTICE phase III study was conducted in patients with mCRC who were ineligible to receive standard full-dose doublet regimens with oxaliplatin or irinotecan and included approximately 13% of patients with low tumour burden [The safety profile of FTD/TPI plus bevacizumab is consistent with that reported in other studies [Although this study did not show noninferiority of FTD/TPI plus bevacizumab to the control group, the FTD/TPI plus bevacizumab regimen remains a promising treatment because the findings suggest its use as third- or later-line treatment. In a randomised, phase II, open-label study of patients receiving therapy for refractory mCRC, treatment with FTD/TPI plus bevacizumab vs. FTD/TPI monotherapy was associated with a significant improvement in PFS (4.6 vs. 2.6 months; HR 0.45; Limitations of the study include the short follow-up period owing to early study termination. A total of 100 patients (39.4%) had a follow-up period of ≤6 months at the time of study discontinuation. In addition, the optimal cutoff for STL was regarded as 60 mm, which had the most significant difference level for OS; however, this cutoff point was not validated. Further analysis is needed to determine whether this cutoff for low tumour burden is appropriate in other studies.In conclusion, our results show that fluoropyrimidine and irinotecan plus bevacizumab remain the standard second-line treatment for mCRC. For patients with low tumour burden, further investigations are warranted to explore more appropriate second-line treatment.