Tanios Bekaii-Saab, MD

Three studies presented at ASCO suggest that an irinotecan-based backbone (FOLFIRI) remains preferred when considering combinations with biologics (VEGF or EGFR inhibitors) in metastatic colorectal cancer (mCRC). The EPOCH trial suggested harmful effects when adding cetuximab to FOLFOX vs. FOLFOX alone in resectable liver-only mCRC. FIRE3 and TRIBE showed very consistent results with FOLFIRI and bevacizumab, with superior survival compared with historical controls. Although TRIBE suggests that the triple drug regimen (FOLFOXIRI) may be superior when added to bevacizumab vs. the doublet, the absence of second-line data limits the interpretation of results.

FIRE3 suggested that the addition of cetuximab to FOLFIRI did not improve overall response rate — the primary endpoint — when compared with bevacizumab added to the same. Median PFS was the same, but OS was surprisingly superior in the cetuximab arm. Again the absence of second-line data presented limits the interpretation of this result, although we are being told more data regarding second-line data will be presented at ESMO World Congress on Gastrointestinal Cancer in early July. Essentially, FIRE 3 should be interpreted as evidence that the two biologics have equivalent activity when added to FOLFIRI in the first-line treatment of mCRC. I think we have now final confirmation that cetuximab should not be combined with FOLFOX, with four negative studies (COIN, NORDIC N0147 and EPOCH) and — in the case of EPOCH — potential harmful effects in KRAS wild-type mCRC patients.

Richard M. Goldberg, MD

In patients who were on the prescribed treatment for only 5 months, the curves for OS didn’t separate until 24 months. It’s really interesting to see a survival curve like this. It’s unprecedented in colon cancer. It suggests that many different regimens contribute to OS, and it’s really not clear whether the first regimen is responsible for all of the benefit or if it’s the interplay of all of the different treatments. In addition, there’s the potential for heterogeneity between groups.

All patients in this study were KRAS wild type. KRAS wild type tells us patients have the potential to respond to cetuximab, but there’s no guarantee that they will. It’s likely there are other biomarkers that we don’t sufficiently understand that could affect whether patients responded to one regimen or the other. All in all, this is good news for patients with colorectal cancer. We’re extending survival beyond 2 years, and many patients are living much longer than that. The field has changed a great deal for the positive over the past 5 years, and we hope to see continuing changes.