Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial

Abstract

Purpose: The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC).Methods: This Phase III, multicenter, randomized, double-blind (patient-and assessor-blind), activecontrolled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m 2 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and

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 .…”

“…The medication regimens of CRC patients are not completely consistent, with the majority of patients receiving one of the bevacizumab biosimilars and reference biologics (5/7.5 mg/kg) in combination with either FOLFIRI (IRI, 5-FU, and LV), FOLFOX (fluorouracil, LV, and oxaliplatin), or XELOX (oxaliplatin and capecitabine). There were three biosimilars [BE1040V ( Rezvani et al, 2020 ), BEVZ92 ( Romera et al, 2018 ), and HLX04 ( Qin et al, 2021 )] in the treatment of CRC. In particular, BEVZ92 (Alymsys TM ) and HLX04 (Hanbeitai TM ) were approved for marketing.…”

“…We assessed ORR and incidence rate of grade 3–5 AEs in three RCTs ( Romera et al, 2018 ; Rezvani et al, 2020 ; Qin et al, 2021 ). Nevertheless, the data of OS were reported only from two RCTs ( Rezvani et al, 2020 ; Qin et al, 2021 ).…”

“…We assessed ORR and incidence rate of grade 3–5 AEs in three RCTs ( Romera et al, 2018 ; Rezvani et al, 2020 ; Qin et al, 2021 ). Nevertheless, the data of OS were reported only from two RCTs ( Rezvani et al, 2020 ; Qin et al, 2021 ). The clinical efficacy (ORR: RR 0.97 [0.87–1.09], p = 0.60, I 2 = 8%, very low certainty, Figure 4A ; OS: HR 0.94 [0.70–1.25], p = 0.66, I 2 = 0, low certainty, Figure 4B ) and safety (AEs: OR 0.78 [0.59–1.02], p = 0.73, I 2 = 0%, low certainty, Figure 4C ) of bevacizumab biosimilars were found to be comparable with reference biologics in CRC patients.…”

Can biosimilar products be interchangeable? Pharmaceutical perspective in the implementation of biosimilars in oncology

“…The non-inferior efficacy and comparable tolerability of another bevacizumab biosimilar (BE1040V) could also be proven in phase III, multicenter, randomized, double-blind study for cases of metastatic colorectal cancer. 70…”