Efficacy and Safety of Bevacizumab Biosimilar FKB238 Versus Originator Bevacizumab: Results from AVANA, a Phase III Trial in Patients with Non-Squamous Non-Small-Cell Lung Cancer (non-sq-NSCLC)

Abstract

Background Bevacizumab is an antiangiogenic recombinant humanized monoclonal antibody that inhibits tumor growth. FKB238, a bevacizumab biosimilar, has analytical pharmacokinetic and safety profiles similar to those of bevacizumab. Objective This phase III trial (NCT02810457) compared the efficacy and safety of FKB238 with that of bevacizumab in patients with advanced/recurrent non-squamous non-small-cell lung cancer (non-sq-NSCLC). Methods This global, multicenter, double-blind, parallel, randomized, comparative clinical trial enrolled and randomized patients with advanced/recurrent non-sq-NSCLC to receive intravenous infusions of either FKB238 15 mg/kg or bevacizumab 15 mg/kg. All patients received intravenous infusions of paclitaxel 200 mg/m 2 and carboplatin (area under the curve 6.0) immediately prior to investigational products for 4-6 cycles. FKB238 and bevacizumab were administered on day 1 of each 21-day cycle until objective progressive disease by RECIST version 1.1 or other discontinuation criteria were met. The primary efficacy endpoint was overall response rate (ORR), including complete and partial response and based on blinded independent central review assessment. Other efficacy determinations included progression-free survival (PFS), overall survival (OS), and immunogenicity. Adverse events and severity were reported. ResultsThe ORR for the intent-to-treat (ITT) population (N = 731) was 51.6% in the FKB238 arm (N = 364) and 53.7% in the bevacizumab arm (N = 367). The FKB238:bevacizumab ORR ratio (ITT population) was 0.96 (90% confidence interval [CI] 0.86-1.08), and the difference in ORR (per-protocol set) between FKB238 and bevacizumab was − 0.02 (95% CI − 0.09 to 0.06). Both CIs fell within the prespecified equivalence margins. Estimated median PFS was 7.72 and 7.62 months in the FKB238 and bevacizumab arms, respectively (hazard ratio 0.97; 95% CI 0.82-1.16). Treatment-emergent adverse events (TEAEs) were reported for 94.2% and 95.1% of patients in the FKB238 and bevacizumab arms, respectively. Grade 3 or higher TEAEs were reported for 53.6% and 55.5% of patients in the FKB238 and bevacizumab arms, respectively. Serious TEAEs were reported for 25.1% and 26.0% of patients treated with FKB238 and bevacizumab, respectively. Conclusions Efficacy equivalence was demonstrated between the two drugs, and safety profiles were similar. There were no meaningful differences in efficacy and safety between FKB238 or bevacizumab in patients with non-sq-NSCLC. Trial registration number NCT02810457.

Efficacy and Safety of Bevacizumab Biosimilars Compared With Reference Biologics in Advanced Non-small Cell Lung Cancer or Metastatic Colorectal Cancer Patients: A Network Meta-Analysis

“…A total of 402 records from the above databases were identified, 17 reports in the full text were reviewed, and 10 RCTs with 5472 patients were deemed eligible for the criteria above ( Figure 1 ) ( Romera et al, 2018 ; Reinmuth et al, 2019 ; Thatcher et al, 2019 ; Yunpeng Yang et al, 2019 ; Reck et al, 2020 ; Rezvani et al, 2020 ; Qin et al, 2021 ; Shi et al, 2021 ; Syrigos et al, 2021 ; Trukhin et al, 2021 ). The baseline characteristics of these trials were summarized in Table 1 .…”

“…For NSCLC, all patients received the same medication regimen: one of the bevacizumab biosimilars or reference biologics (15 mg/kg) along with carboplatin (AUC 6) and paclitaxel (175/200 mg/m 2 ) once 3 weeks. Related biosimilars above mainly involved seven different types, including PF-06439535 (Zirabev TM ) ( Reinmuth et al, 2019 ), ABP 215 (Mvasi TM ) ( Thatcher et al, 2019 ), SB8 (Aybintio TM ) ( Reck et al, 2020 ), FKB238( Syrigos et al, 2021 ), MB02 (Alymsys TM ) ( Trukhin et al, 2021 ), IBI305 (Byvasda TM ) ( Yunpeng Yang et al, 2019 ), and LY01008 (Boyounuo TM ) ( Shi et al, 2021 ). At present, all biosimilars except FKB238 have been approved to market in the clinical environment.…”

“…ORR and incidence rate of grade 3–5 AEs were evaluated in seven RCTs for NSCLC patients ( Reinmuth et al, 2019 ; Thatcher et al, 2019 ; Yunpeng Yang et al, 2019 ; Reck et al, 2020 ; Shi et al, 2021 ; Syrigos et al, 2021 ; Trukhin et al, 2021 ), while the data of PFS and OS were available only by four RCTs ( Reinmuth et al, 2019 ; Reck et al, 2020 ; Syrigos et al, 2021 ; Trukhin et al, 2021 ). The pooled results showed no significant differences in ORR (RR 0.98 [0.92–1.04], p = 0.45, I 2 = 0, low certainty, Figure 2A ), PFS (HR 1.01 [0.92–1.10], p = 0.85, I 2 = 20%, moderate certainty, Figure 2B ), or OS (HR 1.06 [0.94–1.19], p = 0.35, I 2 = 0, moderate certainty, Figure 3A ) between biosimilars and reference biologics in NSCLC patients.…”

“…Concerning NSCLC, a total of seven studies involved in eight treatments were assessed for ORR ( Figure 5A ) ( Reinmuth et al, 2019 ; Thatcher et al, 2019 ; Yunpeng Yang et al, 2019 ; Reck et al, 2020 ; Shi et al, 2021 ; Syrigos et al, 2021 ; Trukhin et al, 2021 ). The results of NMA presented that no significant difference was observed in ORR among any bevacizumab biosimilar for NSCLC patients, which was evaluated with low certainty ( Figure 7A ).…”

“…The results of NMA presented that no significant difference was observed in ORR among any bevacizumab biosimilar for NSCLC patients, which was evaluated with low certainty ( Figure 7A ). Four studies reported the data on PFS and OS ( Figure 5B, C ) ( Reinmuth et al, 2019 ; Reck et al, 2020 ; Syrigos et al, 2021 ; Trukhin et al, 2021 ). SB8, PF-06439535, MB02, and FKB238 were found to exist clinically equivalent survival benefits (moderate certainty; Figure 7B ).…”