Demonstration of Efficacy and Safety Equivalence Between Bevacizumab Biosimilar FKB238 and Bevacizumab Reference in Nonsquamous NSCLC

Phase 3 trial results demonstrate equivalence between the bevacizumab biosimilar FKB238 and bevacizumab reference in terms of efficacy and safety in patients with advanced/recurrent nonsquamous non–small-cell lung cancer (NSCLC).

A comparative global, multicenter, double-blind, parallel, randomized phase 3 trial (NCT02810457) evaluated the efficacy and safety of the bevacizumab biosimilar FKB238 compared with bevacizumab reference + chemotherapy in patients with advanced/recurrent, nonsquamous non–small-cell lung cancer (NSCLC); the results of this trial were reported at the 2020 American Society of Clinical Oncology Virtual Scientific Program.

Eligible patients with advanced/recurrent, nonsquamous NSCLC were randomized to receive FKB238 or bevacizumab reference, at a dose of 15 mg/kg administered by intravenous infusion. Immediately prior to receiving the drugs, all patients received chemotherapy consisting of paclitaxel (200 mg/m²) and carboplatin (area under the curve 6.0) intravenously for 4 to 6 cycles. FKB238 and bevacizumab reference were administered on day 1 of each 21-day cycle until objective progressive disease or other discontinuation criteria were met. The primary end point was objective response rate (ORR) based on blinded independent central review assessment.

A total of 731 patients were enrolled in the study; of these, 364 patients received FKB238 and 367 patients received bevacizumab reference. In the intent-to-treat population, ORR by blinded independent central review assessment was similar between the groups; ORR was 51.6% in the FKB238 arm and 53.7% in the bevacizumab reference arm. The FKB238/bevacizumab reference ORR ratio was 0.96 (90% confidence interval [CI], 0.86-1.08), with the 90% CI contained within the prespecified equivalence margin, thus establishing equivalence between the groups. At 12 months, an estimated 25.0% of patients were alive and progression-free in the FKB238 group compared with 25.3% in the bevacizumab reference group, with an associated hazard ratio of 0.97 (95% CI, 0.82-1.16). The estimated median progression-free survival was similar between the groups, with 7.72 months in the FKB238 group and 7.62 months in the bevacizumab reference group.

Overall, a similar proportion of patients in both arms experienced treatment-emergent adverse events, with 94.2% reported in the FKB238 group and 95.1% reported in the bevacizumab reference group. Treatment-emergent adverse events grade ≥3 (FKB238, 53.6%; bevacizumab reference, 55.5%) and serious adverse events (FKB238, 25.1%; bevacizumab reference, 26.0%) were also similar between the groups.

Based on these results, the authors concluded that equivalence was demonstrated in terms of efficacy and safety between FKB238 and bevacizumab reference in patients with advanced/recurrent, nonsquamous NSCLC.

Reference
Syrigos K, et al. ASCO 2020. Abstract e21728.