Study Finds Biosimilar Bevacizumab Is Bioequivalent to Reference Agent

BEVZ92 is a biosimilar agent in development for the reference agent bevacizumab. Preclinical and in vitro studies suggest that the two products have similar physicochemical and functional properties. A study published in The Lancet Gastroenterology and Hepatology found that the biosimilar and reference product are pharmacokinetically bioequivalent and have no appreciable differences in efficacy, immunogenicity, and safety profiles as first-line treatment in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or fluorouracil, leucovorin, and irinotecan (FOLFIRI) in patients with metastatic colorectal cancer (CRC).

The randomized, open-label trial included adult patients with metastatic CRC with at least one measurable non-irradiated lesion for which first-line chemotherapy was indicated. Patients were included from 15 centers in Argentina, Brazil, India, Spain, and Ukraine. The researchers included patients who had an Eastern Cooperative Oncology Group performance status score ≤2, had not received previous treatment for advanced disease, and whose bone marrow, hepatic, renal, and coagulation markers were all within normal ranges.

A total of 142 patients were randomized 1:1 to receive BEVZ92 (n=71) or reference bevacizumab 5 mg/kg on day one of each cycle every 2 weeks (n=71) in combination with FOLFOX or FOLFIRI. Two patients in the BEVZ92 did not receive treatment: one withdrew consent and the other had a serious intestinal obstruction before starting treatment.

Bioequivalence was established if the 90% confidence intervals (Cis) for the ratio of BEVZ92 to reference bevacizumab of the geometric means for area under the curve_0-336h (AUC) and AUC_ss were within the acceptance interval of 80–125%. In the BEVZ92 cohort, the geometric mean ratio of AUC_0-336h was 99.4% (90% CI = 90.5-109.0) and AUC_ss was 100% (90% CI, 90.2-112.0).

The objective response rate was similar between the BEVZ92 and bevacizumab groups (n=35; 49% vs. n=40; 56%), as was the clinical benefit (n=62; 87% vs. n=65; 92%). The median progression-free survival was also similar: 10.8 months (95% CI, 7.4-11.5) versus 11.1 months (95% CI, 8.0-12.8), respectively.

The researchers observed no relevant differences between the safety profiles of the two study treatments. Neutropenia was the most common grade 3 or 4 adverse event (AE) in the BEVZ92 (n=14; 20%) and bevacizumab (n=19; 27%) groups. Serious AEs occurred in 19 patients (28%) in the BEVZ92 group and 21 patients (30%) in the bevacizumab group.

Two patients died from treatment-related serious AEs, including a sudden death in the BEVZ92 group and a serious large intestinal perforation in the bevacizumab group. Anti-drug antibodies were reported in two patients in the BEVZ92 group and one in the bevacizumab group.