Association between neutropenia and efficacy in patients with refractory mCRC receiving trifluridine/tipiracil + bevacizumab: post hoc analysis of the SUNLIGHT trial

Background

The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared with FTD/TPI for the treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. However, the association between neutropenia and neutrophil count decrease (NCD) and efficacy outcomes in the SUNLIGHT population has not yet been assessed.

Patients and methods

Patients with mCRC enrolled in SUNLIGHT had received no more than two prior treatment regimens and were randomised to receive either FTD/TPI + bevacizumab or FTD/TPI. In this post hoc analysis, overall survival (OS) and progression-free survival (PFS) were analysed in patients with severe (grade ≥3) neutropenia/NCD and in patients with no, or non-severe, neutropenia/NCD.

Results

Patients treated with FTD/TPI + bevacizumab with severe neutropenia/NCD had longer OS (hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.26-0.52] P < 0.0001) and PFS (HR 0.41 [95% CI 0.31-0.55] P < 0.0001) than patients with non-severe or no neutropenia/NCD. Patients treated with FTD/TPI + bevacizumab had improved OS compared with patients treated with FTD/TPI in the severe neutropenia/NCD (HR 0.58 [95% CI 0.40-0.85] P = 0.0046) and non-severe or no neutropenia/NCD (HR 0.71 [95% CI 0.54-0.94] P = 0.0176) subgroups. Most cases of severe neutropenia/NCD occurred during the first two cycles of treatment, did not lead to dose reduction or interruption, and were effectively managed with or without the use of granulocyte colony-stimulating factor.

Conclusions

In SUNLIGHT, patients who developed severe neutropenia/NCD had improved OS and PFS in both treatment arms. Patients receiving FTD/TPI + bevacizumab had longer OS/PFS than patients receiving FTD/TPI, irrespective of the presence of severe neutropenia/NCD.