FOLFOXIRI + cetuximab may not be as crazy as it sounds. But it is every bit as toxic as you'd expect. 🚽 For anyone wondering what might happen if we combined ALL THE THINGS in MSS mCRC, we have the randomized phase II DEEPER: 359 patients with 1L RAS WT mCRC mFOLFOXIRI + cetuximab vs mFOLFOXIRI + bevacizumab Overall: no PFS or OS benefit. Cetuximab with deeper responses: 57.3% vs 46.0%. And in the exploratory left-sided, RAS/BRAF WT subgroup (bear in mind ~30% didn't have known BRAF status): ▪️PFS: 14.8 vs 11.9 months, HR 0.71 ▪️OS: 50.2 vs 40.2 months, HR 0.74 Patients with extrahepatic disease seemed to do better and the effect washed out with liver limited disease: OS 50.2 vs 38.6 months, HR 0.60 Great? But the downside; TRIPLETE already showed us that adding irinotecan to FOLFOX + panitumumab didn't help. What it did do is cause Grade ≥3 diarrhea > 20%. 🚽🚽🚽 So no, triplet + anti-EGFR is not a new standard. But potentially it keys in on some interesting disease biology. And perhaps, once in a blue moon, if someone is feeling exceptionally aggressive with a grossly metastatic, YOUNG, left-sided RAS/BRAF WT patient? Well, maybe... @TheGutOncLab @OncoAlert @Onco_Nexus