A multinational phase II trial of bevacizumab with low-dose interferon-α2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN.

Abstract

BACKGROUND:

Avastin and Roferon in Renal Cell Carcinoma (AVOREN) demonstrated efficacy for bevacizumab plus interferon-α2a (IFN; 9 MIU tiw) in first-line metastatic renal cell carcinoma (mRCC). We evaluated bevacizumab with low-dose IFN in mRCC to determine whether clinical benefit could be maintained with reduced toxicity.

METHODS:

BEVLiN was an open-label, single-arm, multinational, phase II trial. Nephrectomized patients with treatment-naive, clear cell mRCC and favourable/intermediate Memorial Sloan-Kettering Cancer Center scores received bevacizumab (10 mg/kg every 2 weeks) and IFN (3 MIU thrice weekly) until disease progression. Descriptive comparisons with AVOREN patients having favourable/intermediate MSKCC scores treated with bevacizumab plus IFN (9 MIU) were made. Primary end points were grade ≥3 IFN-associated adverse events (AEs) and progression-free survival (PFS). All grade ≥3 AEs and bevacizumab/IFN-related grade 1-2 AEs occurring from first administration until 28 days after last treatment were reported.

RESULTS:

A total of 146 patients were treated; the median follow-up was 29.4 months. Any-grade and grade ≥3 IFN-associated AEs occurred in 53.4% and 10.3% of patients, respectively. The median PFS and overall survival were 15.3 [95% confidence interval (CI): 11.7-18.0] and 30.7 months (95% CI: 25.7-not reached), respectively. The ORR was 28.8%.

CONCLUSIONS:

Compared with a historical control AVOREN subgroup, low-dose IFN with bevacizumab resulted in a reduction in incidence rates of IFN-related AEs, without compromising efficacy [NCT00796757].

• Authors: B Melichar, S Bracarda, V Matveev, B Alekseev, S Ivanov, A Zyryanov, R Janciauskiene, E Fernebro, P Mulders, S Osborne, S Jethwa, G Mickisch, M Gore, R J A van Moorselaar, M Staehler, N Magne, J Bellmunt, BEVLiN Investigators
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 24 Issue 9 Pg. 2396-402 (Sep 2013) ISSN: 1569-8041 [Electronic] England
• PMID: 23803225 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Bevacizumab

Topics

• Adult
• Angiogenesis Inhibitors (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab
• Carcinoma, Renal Cell (drug therapy, mortality)
• Disease-Free Survival
• Female
• Humans
• Immunotherapy
• Interferon alpha-2
• Interferon-alpha (administration & dosage, therapeutic use)
• Kidney Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• Neovascularization, Pathologic (drug therapy)
• Recombinant Proteins (administration & dosage, therapeutic use)
• Treatment Outcome
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)
• Young Adult