Dual anti-angiogenesis agents bevacizumab plus trebananib, without chemotherapy, in first-line treatment of metastatic colorectal cancer: results of a phase II study.

Purpose To assess the efficacy and safety of dual anti-angiogenesis agents, bevacizumab plus trebananib, without chemotherapy, in first-line treatment of metastatic colorectal cancer (mCRC). Experimental design Open label Phase II study enrolled patients with unresectable mCRC with no prior systemic treatment. All patients received bevacizumab 7.5mg/kg 3-weekly and trebananib 15 mg/kg weekly. The primary endpoint was disease control (stable disease, partial (PR) or complete responses (CR)) at 6 months (DC6m). Secondary endpoints included toxicity, response rate (ORR), progression-free survival (PFS) and overall survival (OS). Exploratory biomarkers in plasma angiogenesis-related proteins, tumour gene expression and plasma antibodies to tumour antigens were examined. Results 45 patients were enrolled from four Australian sites. DC6m was 63% (95% CI: 47-77). ORR was 17% (95% CI: 7-32), comprising 7 PRs. Median duration of response was 20 months (range 10-48 months). Median PFS was 8.4 months and median OS 31.4 months. G1-2 peripheral oedema and joint-related symptoms were common. Overall incidence of G3-4 adverse events (AEs) of any type was 33% (n=15). Expected AEs of bevacizumab treatment did not appear to be increased by the addition of trebananib. Conclusions In a first-line mCRC population, the dual anti-angiogenic combination, bevacizumab plus trebananib, was efficacious with durable responses. The toxicity profile of the combination was manageable and did not exceed that expected with bevacizumab +/-chemotherapy. Exploratory biomarker results suggest that in addition to its anti-angiogenic activity, this combination may provide clinical benefit by enabling anti-tumour immunomodulatory effects, supporting ongoing trials of anti-angiogenic therapy combined with cancer immunotherapy.