5-fluorouracil plus bevacizumab plus anakinra for patients with metastatic colorectal cancer refractory to standard therapies (IRAFU): An investigator-initiated, open-label, single-arm, multicentre, phase 2 study.

Abstract

e15540 Background: In patients with metastatic colorectal cancer resistant to chemotherapy few therapeutic option are available. In preclinical models, we show that IL-1b inhibition enhance efficacy of 5-fluorouracil by inhibiting IL-17A dependent tumor neoangiogenesis. In this phase 2 study, we assessed the activity and safety of 5-fluorouracil plus bevacizumab plus anakinra (an IL-1 inhibitor) in patients refractory to classical chemotherapies. Methods: We did this investigator-initiated, open-label, single-arm, multicenter, phase 2 trial of 5-fluorouracil plus bevacizumab plus anakinra in two French centers. Eligible patients were aged 20 years or older; had histologically confirmed unresectable, metastatic colorectal adenocarcinoma; were refractory to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy. Patients were treated with simplified LV5FU regimen and bevacizumab (5 mg/kg) both administered by intravenous infusion for 30 min every 2 weeks. Anakinra (100mg) was administrated by subcutaneous injection daily. The primary endpoint was 2 months response rate determined upon CHOI criteria. Results: Between October 06, 2014, and May 15, 2017, we enrolled 32 patients with metastatic colorectal cancer. Five patients have response rate upon Choi criteria and 22 patients had stable disease as the best overall response. Median progression-free survival and overall survival were 5.4 and 14.5 months, respectively. Twenty patients experiment grade 3 toxicity. No grade 4 or 5 toxicity related to therapy occurred. The most common grade 3 adverse events were neutropenia (8 [25%] patients), digestive (7 [21.88%] patients) and hypertension (6 [18.75%] patients). Biological study underline that the treatment limits tumor neoangiogenesis and impact Th1/Th17 ratio. Conclusions: 5-fluororuracil plus bevacizumab and anakinra has promising activity with few and manageable safety profile, suggesting that this combination might become a potential treatment option for patients with metastatic colorectal cancer in a refractory setting. Clinical trial information: NCT02090101.