BCD-021 has demonstrated equivalence to Avastin® (bevacizumab) in a comprehensive comparability exercise that included physicochemical, PK and PD studies, as well as a phase 1 PK clinical study in patients with nonsquamous NSCLC.a Now, Filon and colleaguesb presented results from a multicenter, double-blind, randomized, phase 3 study of 138 patients with advanced nonsquamous NSCLC (stage IIIb/IV) who were randomly assigned 1:1 to receive BCD-021 or Avastin at a dose of 15 mg/kg in combination with paclitaxel (175 mg/m2) and carboplatin (AUC 6 mg/ml×min) every 3 weeks, up to 6 cycles of therapy or until disease progression or unbearable toxicity. The primary endpoint was objective response rate (ORR).
There was no statistically significant difference in ORR between the groups: 42.6% (95% CI 30.33 – 55.83) in the BCD-021 group and 39.3% (95% CI 27.58 – 52.27%) in the Avastin group. The lower limit of 95% CI for ORR difference between the groups (-14.96%) did not exceed the noninferiority margin; hence BCD-021 was judged as noninferior to Avastin. There were also no differences between the groups for all other efficacy parameters: Complete remission (1.9% vs 1.8%), partial remission (40.7% vs 37.5%), stable disease (51.8%vs 51.8%), and rate of progression (5.6% vs 8.9%) in the BCD-021 and Avastin groups, respectively. Adverse event (AE) profiles of BCD-021 and Avastin were equivalent; the rate of all observed AEs including severe AEs showed no statistically significant differences between the groups. Most AEs were associated with the chemotherapy: neutropenia, anemia, leukopenia, thrombocytopenia, hyperglycemia, increased LDH, increased alkaline phosphatase, increased ALT, and alopecia. AEs specific for bevacizumab included arterial hypertension, weakness, lung bleeding, proteinuria, gastrointestinal perforation, and venous thromboembolism. Binding and neutralizing antibodies were transient and detected in only 1 patient in each group, indicating the low immunogenic potential of both drugs. This study showed that BCD-021 demonstrated noninferiority to the innovator bevacizumab in patients with nonsquamous NSCLC and may be a suitable biosimilar for Avastin in these patients.
