FOLFOXIRI/bevacizumab (bev) versus doublets/bev as initial therapy of unresectable liver-only, right-sided and/or RAS or BRAF mutated (mut) metastatic colorectal cancer (mCRC): An individual patient data-based pooled analysis of randomized trials.

e15563 Background: FOLFOXIRI/bev was associated with longer PFS and OS versus doublets/bev independently of the presence of liver-limited disease or not, and the secondary resection of metastatic lesions. Recently, in the CAIRO-5 study patients with liver-limited right-sided and/or RAS or BRAF mutated mCRC experienced no OS difference, but higher ORR, R0 resection rate, and longer PFS with the triplet/bev when compared with doublets/bev. Here we aim at providing an estimation of the efficacy and activity of FOLFOXIRI/bev over doublets/bev in patients with unresectable liver-only, right-sided and/or RAS or BRAF mut mCRC. Methods: We selected pts with liver-only, right-sided and/or RAS or BRAF mut mCRC, and treated with first-line doublets/bev or FOLFOXIRI/bev in four phase II or III randomized controlled trials (RCTs): TRIBE (NCT00719797), TRIBE2 (NCT02339116), CHARTA (NCT01321957), and STEAM (NCT01765582). Patients included in these RCTs were deemed initially unresectable according to a 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: A total of 300 pts were eligible. The median age was 61 years and most of them had an ECOG performance status of 0 (83%) and synchronous metastases (91%). One hundred and thirty (43%) and 170 (57%) pts received doublets/bev and FOLFOXIRI/bev, respectively. Baseline characteristics were homogeneous between the two treatment groups. Pts receiving FOLFOXIRI/bev showed longer PFS (12.3 vs 10.3 months mos HR:0.75, p = 0.019) and a statistically not significant trend for better OS (29.1 vs 23.2 mos, HR:0.85, p = 0.253), than those treated with doublets/bev. FOLFOXIRI/bev was also associated with higher ORR (64% vs 53%, OR:1.54, p = 0.076) and no differences in R0 resection rate (27% vs 24%, OR:1.15, p = 0.696) was reported. No significant interaction was found between treatment effect and the achievement of R0 resection in terms of both PFS (P interaction :0.81) and OS (P interaction :0.53). Conclusions: As compared to doublets/bev, upfront FOLFOXIRI/bev provides a meaningful advantage to pts with initially unresectable, liver-only, right-sided and/or RAS or BRAF mut mCRC, in terms of activity and efficacy, thus corroborating the choice of this regimen as upfront treatment for these pts, regardless of the opportunity to achieve the R0 secondary resection of their liver metastatic lesions.