Two phases III studies (FIRE-3 and CALGB/SWOG80405) suggested higher response rate (RR) for doublet chemotherapy with an anti-EGFR (Epidermal Growth Factor Receptor) compared to an anti-VEGF (Vascular Endothelial Growth Factor), in first line RAS/BRAF wild-type (WT) unresectable metastatic colorectal cancer (mCRC). Unfortunately, in clinical practice the delay to obtain RAS/BRAF status may delay the chemotherapy start. No study has evaluated the impact of a delayed introduction of the anti-EGFR.
This retrospective multicentric AGEO (Association Gastro-Entérologues Oncologues) study included mCRC RAS/BRAF WT patients who received a doublet chemotherapy either with an anti-VEGF introduced immediately (control arm) or with an anti-EGFR introduced at cycle 2 or 3 (delayed group) between 2013 and 2016. The primary endpoint was the Progression Free Survival (PFS). The Overall Survival (OS) and the RR were secondary endpoints. Given different characteristics between the two groups, a propensity score was developed.
A total of 262 patients were included: 129 in the control group and 133 in the delayed group. Compared to the delayed group, patients treated in the control group were more likely descendant mCRC (60% vs 44%) and had more metastatic sites (>1 site: 57% vs 40%). In the delayed anti-EGFR group, the time to obtain RAS status was 20.7 days ±18.9. The anti-EGFR was introduced in 70% of cases at C2 and in 30% at C3. Using the propensity score, there was no more difference between the two groups. The median follow-up was 37.9 months. PFS and RR were significantly longer and higher in the delayed anti-EGFR group compared to the control anti-VEGF group (PFS: 13.8 vs 10.8 months, p = 0.03; RR: 67% vs 46%, p = 0.0007). Meantime, no difference was observed concerning OS (30.4 months vs 30.0 months, p = 0.23).
There is no deleterious effect of delayed anti-EGFR introduction at cycle 2 or 3 compared to the immediate introduction of anti-VEGF in patients with RAS/BRAF WT mCRC. Therefore, in current clinical practice, if the response rate is an important goal, it is possible to wait for RAS status and to initially start chemotherapy without targeted therapy.
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D. Tougeron: Consulting or advisory role: MSD, BMS, Sanofi, Roche; Speaker’s bureau: Roche, Novartis, Servier; Travel, accomodations, expenses: MSD, BMS, Merck, Amgen. A. Lievre: Consulting or advisory role: Merck, Amgen, Bayer, Ipsen; Speaker’s bureau: Roche, Merck, Ipsen, BMS, Novartis, Servier; Travel, accomodations, expenses: Merck, Novartis, Ipsen, Roche. S. Pernot: Honoraria: Amgen, Sanofi; Travel, accomodations, expenses: Amgen, Merck, Servier, Bayer. O. Bouche: Consulting or advisory role: Roche, Merck, Amgen, Bayer; Speaker’s bureau: Lilly, Pierre Fabre, Novartis, Servier; Travel, accomodations, expenses: Lilly, Roche, Merck. R. Coriat: Amgen, Merck, Roche, Novartis, Ipsen, Keocyt, Bayer, Servier. All other authors have declared no conflicts of interest.