Abstract
Simple SummaryThe first-line therapy of patients with RAS wild-type (WT) non-resectable metastatic colorectal cancer (mCRC) is usually 5-fluorouracil-based chemotherapy with either bevacizumab or an anti-epidermal growth factor receptor (EGFR). The introduction of anti-epidermal growth factor antibodies is commonly delayed because of late RAS testing results. Our objective was to evaluate the impact on the overall survival of delayed anti-EGFR introduction strategy. This study compared 305 patients with delayed anti-EGFR introductions, 401 with immediate anti-EGFRs, and 129 with immediate anti-VEGFs. The study suggests that delayed introduction has no deleterious impact on survival compared to the immediate introduction of an anti-EGFR or of an anti-VEGF. The first-line therapy of patients with RAS wild-type (WT) non-resectable metastatic colorectal cancer (mCRC) is usually 5-fluorouracil-based chemotherapy with either bevacizumab or an anti-epidermal growth factor receptor (EGFR). The addition of anti-EGFR antibodies is commonly delayed in clinical practice because of late RAS testing results. Our objective was to evaluate the impact on overall survival (OS) of a delayed anti-EGFR introduction strategy. This study pooled the data of two large retrospective studies. Patients with RAS WT non-resectable mCRC, treated in first line by a doublet chemotherapy with an anti-EGFR introduced with a delay of 2 to 4 cycles, were compared to an anti-EGFR and to an anti-VEGF that was introduced immediately. Patients numbering 305 in the delayed anti-EGFR group, 401 in the immediate anti-EGFR group, and 129 in the immediate anti-VEGF group were analyzed. After propensity scoring, there was no difference between the characteristics of the three groups. Median OS was 28.6 months (95% CI: 23.5–34.1) in the immediate anti-EGFR group, 35.1 (95% CI: 29.9–43.5) in the delayed anti-EGFR group, and 32.4 (95% CI: 25.4–44.8) in the immediate anti-VEGF group. There was no significant difference concerning median OS (p = 0.24) or progression-free survival (p = 0.56). This study suggests that delaying the introduction of an anti-EGFR has no deleterious impact on survival compared to the immediate introduction of an anti-VEGF or of an anti-EGFR.
Highlights
Colorectal cancer was the third most frequent cancer and the second cause of cancerrelated mortality worldwide in 2020, with an estimated mortality rate of up to 577,000 deaths per year [1]
Three groups were compared: anti-epidermal growth factor receptor (EGFR) added to chemotherapy at first cycle (N = 401), antiEGFR added to chemotherapy at cycle 2 (N = 71), and anti-EGFR added to the chemotherapy at cycle 3 or 4 (N = 101)
The immediate introduction of an anti-VEGF started at first cycle (N = 129) was compared to the delayed introduction of an anti-EGFR started at cycle 2 or 3 (N = 133)
Summary
Colorectal cancer was the third most frequent cancer and the second cause of cancerrelated mortality worldwide in 2020, with an estimated mortality rate of up to 577,000 deaths per year [1]. The high predictive value of KRAS mutations in response to cetuximab was proved in 2008 [6] This was later confirmed and completed with extended mutations in KRAS and NRAS exons 2, 3, and 4 [7–9]. These results led to the recommendation of obtaining RAS status before the introduction of an anti-EGFR in first-line chemotherapy for RAS WT mCRC. Oncologists often initiate doublet chemotherapy without any monoclonal antibody and subsequently introduce anti-EGFR when the WT RAS status is available. Another option is not to wait and use doublet chemotherapy with bevacizumab up front
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