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Treatment outcome comparisons of first-line targeted therapy in patients with KRAS wild-type metastatic colorectal cancer: A nationwide database study
Background
It remains controversial regarding whether bevacizumab or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) is the better companion of a chemotherapy doublet as the first-line treatment for inoperable KRAS wild-type metastatic colorectal cancer (mCRC).
Methods
We established a cohort of patients with KRAS wild-type mCRC who initiated first-line targeted therapy plus doublet chemotherapy between 2013 and 2018 from the database of National Health Insurance, Taiwan. Patients were classified according to the targeted therapy agents used in the first-line treatment regimen into the bevacizumab group and the anti-EGFR mAb group. The definition of secondary surgeries included resections of primary tumors, liver metastases, or lung metastases and radiofrequency ablation.
Results
A total of 6,482 patients were included; the first-line targeted therapy was bevacizumab and anti-EGFR mAb in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Patients who received anti-EGFR mAb, compared with patients who received bevacizumab, exhibited significantly longer overall survival (OS) (median, 23.1 vs. 20.2 months, p = 0.012) and time-to-treatment failure (TTF) (median, 11.3 vs. 10.0 months, p < 0.001). We further analyzed the treatment outcomes according to the sidedness of the primary tumor. Among patients with left-sided mCRC, those who received anti-EGFR mAb in first-line systemic therapy, compared with those who received bevacizumab, exhibited significant longer OS (median, 24.9 vs. 22.9 months, p = 0.021) and TTF (median, 12.2 vs. 10.4 months, p < 0.001). Among patients with right-sided mCRC, those who received anti-EGFR mAb and those who received bevacizumab in first-line systemic therapy exhibited similar OS (median, 15.6 vs. 16.1 months, p = 0.385) and TTF (median, 7.6 vs. 8.8 months, p = 0.146). In the multivariate analyses, first-line anti-EGFR mAb remained an independent predictor for longer OS and TTF for left-sided primary tumors. Among the 6,482 patients in the study, 1,685 (26.0%) received secondary surgeries after initiation of the first-line systemic therapy. Patients who received secondary surgeries exhibited significantly longer OS than patients who never received secondary surgeries (median, 37.9 vs. 17.2 months, p < 0.001). Patients who received anti-EGFR mAb were more likely to receive secondary surgeries (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab.
Conclusions
In this nationwide cohort study, we demonstrated that among patients who received first-line chemotherapy doublets for inoperable KRAS wild-type mCRC, the combination with anti-EGFR mAb, compared with the combination with bevacizumab, led to significantly longer OS and TTF. This benefit mainly came from patients with left-sided primary tumors. In the multivariate analysis, anti-EGFR mAb treatment remained an independent predictor of longer OS and TTF for the left-sided primary tumors. To our knowledge, this is the largest (n = 6,482) cohort study focusing on this issue.
Legal entity responsible for the study
The authors.
Funding
This study was supported by the Ministry of Science and Technology, Taiwan (MOST 105-2314-B-002-194, MOST 106-2314-B-002-213, and MOST 108-2314-B-002-072-MY3); National Taiwan University Hospital, Taipei, Taiwan (NTUH.105-S2954, NTUH, 108-S4150); and the Science and Technology Unit, Ministry of Health and Welfare, Taiwan (DOH102-NH-9002). We would like to acknowledge the service provided by the RCF5 Lab. of Department of Medical Research at National Taiwan University Hospital.
Disclosures
All authors have declared no conflicts of interest.
