Background. The registered AVOREN Phase III trial demonstrated the efficacy of a combination of bevacizumab and interferon-α (IFN-α) as first-line targeted therapy in patients with metastatic renal-cell cancer (mRCC). The median progression-free survival (PFS) was significantly higher in the bevacizumab + IFN-α group, amounting to 10.2 months versus 5.4 months in the IFN-α group (p < 0.0001). The most common grade 3 and 4 side effects in the AVOREN study included the adverse events due to IFN-α use; this initiated a prospective multicenter BEVLiN (Bevacizumab and Low-Dose Interferon) Phase II trial in 2008 to evaluate the efficacy and tolerability of a combination of bevacizumab and low-dose IFN-α in patients with mRCC to diminish the toxicity of treatment.

Subjects and methods. The trial enrolled 146 patients having good and moderate prognosis according to the MSKCC scale. The patients received Avastin 10 mg/kg every 2 weeks and IFN-α 3,000,000 IU thrice weekly. The historical control group was taken from the AVOREN trial as a control group. The main purposes of the trial were to evaluate the tolerability of treatment (the frequency of adverse events due to IFN-α use, grade 3 or more toxicity) and PFS. The additional goals were to estimate overall survival (OS), objective response rates, and the incidence of any adverse events of grade 3–4 toxicity.

Results. The median follow-up was 29.4 months (range 1.5–35.4 months). The rate of objective responses was 28.8 % (95 % confidence interval (CI) 21.4–37.1). The median PFS was 15.3 months (95 % CI 11.7–18.0) and PFS was 58.2 and 28.9 % at 12 and 24 months of treatment, respectively. The median OS was 30.7 months (95 % CI 25.7 was unachieved). In the IFN-α group, all grades of adverse reactions and their grade 3 or more were recorded in 53.4 and 10.3 % of the patients, respectively. The adverse events that were a reason for IFN-α discontinuation were recorded in 24.0 % of the patients.

Conclusion. The BEVLiN trial has shown that IFN-α dose decrease can substantially reduce the frequency of side effects, without worsening PFS and OS rates.