FOLFOXIRI (triplet chemo) + capecitabine-RT delivers 20.5% pCR in high-risk LARC

Modified FOLFOXIRI (5-FU/leucovorin, oxaliplatin, irinotecan) induction chemotherapy was tested as part of a Phase II, multicenter, single-arm total neoadjuvant approach in Chinese patients with high-risk, non-metastatic rectal adenocarcinoma (T3/T4 ± nodes; threatened circumferential resection margin and/or sphincter involvement) (n=40; 39 evaluable; NCT01941641). After 4 cycles of FOLFOXIRI then concurrent capecitabine-radiotherapy and surgery, ORR was 30.8% after induction and 64.1% after CRT, with 71.8% TNM downstaging; pCR was 20.5% and 30 patients achieved negative CRM—broadly in the expected pCR range for fluoropyrimidine-based CRT intensification/TNT strategies (~14–30%), and modestly below the ~26–28% pCR reported with modern TNT regimens like PRODIGE-23. Grade 3–4 AEs were mainly diarrhea (13%), neutropenia (8%), and vomiting (5%) during FOLFOXIRI; during CRT, grade 3–4 events were each 3% (diarrhea, rectal hemorrhage, sexual dysfunction); with median follow-up 72.7 months, 3-year/5-year OS was 79.5%/59.5% and 3-year RFS 72.4%, while high IGF2 expression associated with worse DFS (p=0.0176) but not OS.