Abstract 63P
Background
FOLFOXIRI/bev was associated with longer PFS and OS vs doublets/bev independently of the presence of LL disease and the secondary resection of metastatic lesions. In the CAIRO-5 trial pts with LL right-sided and/or RAS or BRAF mut mCRC experienced no OS difference, but higher ORR, R0 resection rate and longer PFS with the triplet/bev compared with doublets/bev. Here we aim at providing an estimation of the efficacy and activity of FOLFOXIRI/bev over doublets/bev in pts with unresectable LL, right-sided and/or RAS or BRAF mut mCRC.
Methods
We selected pts with LL, right-sided and/or RAS or BRAF mut mCRC, treated with upfront doublets/bev or FOLFOXIRI/bev in 4 phase II/III RCTs: TRIBE, TRIBE2, CHARTA and STEAM. Pts were deemed initially unresectable according to multidisciplinary evaluation and were not selected based on the potential conversion to resectability. We compared FOLFOXIRI/bev with doublets/bev in terms of PFS, OS, ORR, and R0 resection.
Results
Of 300 eligible pts, median age was 61 and most of them had an ECOG PS of 0 (83%) and synchronous metastases (91%). 130 (43%) and 170 (57%) pts received doublets/bev and FOLFOXIRI/bev, respectively. Baseline characteristics were homogeneous between groups. Pts receiving FOLFOXIRI/bev showed longer PFS (12.3 vs 10.3 months [mos] HR:0.75, p = 0.02) and a statistically not significant trend for better OS (29.1 vs 23.2 mos, HR:0.85, p = 0.25), than those treated with doublets/bev. FOLFOXIRI/bev was associated with higher ORR (64% vs 53%, OR:1.54, p = 0.08) but no differences in R0 resection rate (27% vs 24%, OR:1.15, p = 0.70). No significant interaction was found between treatment effect and the achievement of R0 resection in terms of both PFS (Pint=0.81) and OS (Pint=0.53).
Conclusions
As compared to doublets/bev, FOLFOXIRI/bev provides a meaningful advantage to pts with initially unresectable, LL, right-sided and/or RAS or BRAF mut mCRC, in terms of activity and efficacy, thus corroborating the choice of triplet as upfront therapy for these pts, regardless of the opportunity to achieve the R0 secondary resection of their liver metastatic lesions.
Legal entity responsible for the study
GONO Foundation.
Funding
Has not received any funding.
Disclosure
D. Rossini: Financial Interests, Personal, Other, Honoraria: Takeda Pharmaceuticals. C. Cremolini: Financial Interests, Personal, Other, Honoraria: Amgen, Bayer, Merck, Roche, and Servier; Financial Interests, Institutional, Advisory Board: Amgen, Bayer, MSD, and Roche; Financial Interests, Institutional, Speaker’s Bureau: Servier; Financial Interests, Institutional, Funding: Bayer, Merck, and Servier. All other authors have declared no conflicts of interest.