SIRFLOX: Differences in site of first progression between mFOLFOX6 +/- bevacizumab (bev) versus mFOLFOX6 +/- bev + selective internal radiation therapy (SIRT) in first-line patients (pts) with metastatic colorectal cancer (mCRC).

Abstract

Background: SIRFLOX, an international multi-centre open-label RCT in first-line pts with non-resectable, liver-only or liver-dominant mCRC, showed that compared to FOLFOX (+/- bev) chemotherapy alone [arm A] FOLFOX (+/- bev) plus SIRT using Y-90 resin microspheres [arm B] did not improve overall PFS (median 10.2 v 10.7 months arm A v B, HR: 0.93; 95% CI 0.77-1.12; p = 0.429). However, liver PFS by competing risk analysis was improved with the addition of SIRT (median 12.6 v 20.5 months in arm A v B, HR: 0.69; 95% CI 0.55-0.90; p = 0.002). The current analysis examines patterns of disease progression and potential impact on the primary study endpoint. Method(s): Site and pattern (intra/extra-hepatic) of first progression, and whether progression was due to growth of existing lesions or the appearance of new lesions, was judged by an independent reader blinded to study arm. Result(s): From Oct 2006 to Apr 2013, 530 pts were randomised (arm A, n = 263; arm B, n = 267); 212 (40%) had extra-hepatic metastases at study entry; 292 (55%) were stratified to receive bev. As of 31 Jan 2015, the total number of patients with disease progression in arm A v B were 178 and 166, respectively. The site of first progression was more frequently in the liver (+/- other sites) in arm A v B (92.1% v 72.3%; p < 0.001). Conversely, site of first progression was less frequent in the lung (+/- other sites) in arm A v B (19.1% v 42.8%; p < 0.001). A higher proportion of first progression occurred in the liver alone in arm A v B (77.0% v 52.4%; p < 0.001). Conversely, a lower proportion of first progression occurred only in non-liver sites, primarily lung, in arm A v B (7.9% v 47.7%; p < 0.001). Of patients with first progression in the liver, a higher proportion occurred in existing liver lesions (+/- extrahepatic sites) in arm A v B (72.5% v48.2%; p < 0.001). Conclusion(s): The addition of SIRT to FOLFOX chemotherapy alone (+/- bev) reduced the frequency at which first disease progression occurred in the liver. Where first progression did occur in the liver, the addition of SIRT led to this more frequently being due to the appearance of lesions not evident on baseline imaging.