Abstract
The primary tumour location is an important prognostic factor for previously untreated metastatic colorectal cancer (mCRC). However, the predictive efficacies of primary tumour location, early tumour shrinkage (ETS), and depth of response (DpR) on mCRC treatment has not been fully evaluated. This study aimed to investigate the predictive efficacies of these traits in mCRC patients treated with first-line 5-fluorouracil-based chemotherapy plus biologic agents, namely, cetuximab and bevacizumab. This was a retrospective analysis of the medical records of 110 patients with pathology-documented unresectable mCRC. Patients with left-sided mCRC receiving any first-line regimen showed better overall survival (OS) than those with right-sided mCRC [33.3 vs 16.3 months; hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27–0.74; p < 0.001]. In patients with left-sided tumours, treatment with chemotherapy plus cetuximab yielded longer OS than chemotherapy plus bevacizumab (50.6 vs 27.8 months, HR 0.55; 95% CI 0.32–0.97; p = 0.0378). mCRC patients with ETS and high DpR showed better OS than those lacking ETS and with low DpR (33.5 vs 19.6 months, HR 0.50, 95% CI 0.32–0.79, p = 0.023 and 38.3 vs 19.0 months, HR 0.43, 95% CI 0.28–0.68, p < 0.001, respectively). Moreover, ETS and/or high DpR achieved in patients with right-sided mCRC receiving chemotherapy plus cetuximab were associated with significantly better OS than in those lacking ETS and with low DpR (34.3 vs 10.4 months, HR 0.19, 95% CI 0.04–0.94, p = 0.025 and 34.3 vs 10.4 months, HR 0.19, 95% CI 0.04–0.94, p = 0.0257, respectively). Taken together, our study demonstrates that primary tumour location is not only a well-known prognostic factor but also a relevant predictive factor in patients with mCRC receiving chemotherapy plus cetuximab. Additionally, both ETS and DpR could predict treatment outcomes and also potentially guide cetuximab treatment even in right-sided mCRCs.
Highlights
The primary tumour location is an important prognostic factor for previously untreated metastatic colorectal cancer
In the pooled analysis of six randomised trials, metastatic colorectal cancer (mCRC) patients with left-sided tumours harbouring RAS wt status showed favourable overall response rate (ORR), overall survival (OS), and progression-free survival (PFS) than those with right-sided tumours, and the analyses predicted better response upon treatment with chemotherapy plus anti-epidermal growth factor receptor (EGFR) therapy than chemotherapy alone or chemotherapy plus anti-vascular endothelial growth factor (VEGF) therapy[18]. These findings suggest that the location of tumours on the left side can help predict the efficacy of anti-EGFR antibodies in mCRC patients with KRAS wt status
Here, we investigated the prognostic and predictive efficacy of primary tumour location and the impact of early tumour shrinkage (ETS) and/or depth of response (DpR) on therapeutic outcomes in a cohort of patients with mCRC treated with first-line chemotherapy plus bevacizumab or cetuximab in the real-world setting in a Japanese population
Summary
The primary tumour location is an important prognostic factor for previously untreated metastatic colorectal cancer (mCRC). In the pooled analysis of six randomised trials, mCRC patients with left-sided tumours harbouring RAS wt status showed favourable ORR, OS, and PFS than those with right-sided tumours, and the analyses predicted better response upon treatment with chemotherapy plus anti-EGFR therapy than chemotherapy alone or chemotherapy plus anti-VEGF therapy[18]. Taken together, these findings suggest that the location of tumours on the left side can help predict the efficacy of anti-EGFR antibodies in mCRC patients with KRAS wt status
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