Clinical and Molecular Predictors of Early Tumor Shrinkage and Depth of Response in Metastatic Colorectal Cancer Treated with mFOLFOXIRI plus Bevacizumab: A Retrospective Study from Vietnam
Anh Tuan Pham, Ngan Thi Kim Mai, Trinh Le Huy, Hau Xuan Nguyen, Hung Van Nguyen, Anh Dinh Tran, Thao Thi Phuong NguyenBackground
Early tumor shrinkage (ETS) and depth of response (DpR) are increasingly recognized as early efficacy endpoints and potential surrogate markers of long-term outcomes in metastatic colorectal cancer (mCRC). However, determinants of ETS and DpR in patients receiving intensive first-line chemotherapy remain insufficiently characterized, particularly in Asian populations.
Methods
We retrospectively analyzed patients with histologically confirmed mCRC treated with first-line mFOLFOXIRI plus bevacizumab at Hanoi Medical University Hospital between January 2020 and June 2025. ETS was defined as a ≥20% reduction in target lesion diameters at the first radiological assessment (8 weeks), and DpR as the maximum percentage reduction from baseline. Logistic and linear regression were used to identify factors associated with ETS and DpR. PFS was analyzed according to ETS and DpR.
Results
Seventy-two patients were included. ETS was observed in 56.9%, with a median DpR of 40% and median time to maximal response of 4.9 months. Primary tumor resection showed a trend toward higher ETS rates in multivariable analysis, whereas no patient with a BRAF V600E mutation achieved ETS, although the number of BRAF-mutant tumors was limited. ETS was significantly associated with greater DpR. In multivariable analysis, ETS, completion of 12 treatment cycles, and ≥50% CEA reduction at week 8 were associated with greater DpR. RAS, BRAF, and PIK3CA mutations were not independently associated with DpR. Median PFS was 14.5 months, with significantly longer PFS in patients achieving ETS or higher DpR.
Conclusions
In patients with metastatic colorectal cancer treated with first-line mFOLFOXIRI plus bevacizumab, ETS and early CEA reduction were associated with greater tumor shrinkage. Both ETS and DpR were also associated with longer progression-free survival, supporting their potential role as early markers of treatment response.