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Meta-analysis Confirms Biosimilarity Between Bevacizumab Biosimilars, Avastin in NSCLC, Colorectal Cancer


The efficacy and safety of bevacizumab biosimilars in advanced non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (CRC) is comparable with the reference product (Avastin) and each other, according to a meta-analysis.

The efficacy and safety of bevacizumab biosimilars in patients with advanced non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (CRC) was comparable with those of the reference biologic and each other, according to a meta-analysis published in Frontiers in Pharmacology.

Lung and colorectal cancers are the second and third most common cancers, the authors said, and the leading and second leading causes of death from cancer worldwide. Bevacizumab is an antibody targeting vascular endothelial growth factor (VEGF), preventing it from interacting with receptors on the surface of endothelial cells.

The reference product (Avastin) was first approved for treatment of metastatic CRC in 2004. Currently, the authors said bevacizumab plus platinum-based chemotherapy is a first-line treatment for multiple cancers, including NSCLC and CRC in the United States, European Union, and China.

Biosimilars referencing bevacizumab “are slowly making their way into cancer treatment, but the data on their efficacy and safety in cancer patients are still poor,” according to the authors. The first bevacizumab biosimilar, ABP 215 (Mvasi) was approved by the FDA in 2017 for treating NSCLC. There are currently 4 bevacizumab biosimilars approved in the United States, 8 in China, and 8 in the European Union.

The authors said their analyses aimed to summarize the data on equivalence studies and compare biosimilars to one another, to help clinicians and payers make informed decisions when a variety of biosimilars are available. Ten total trials including 5526 patients met their eligibility criteria, 7 trials (4581 patients) in NSCLC and 3 (945 patients) in CRC.

The authors used pairwise meta-analysis to compare each biosimilar to the reference product, and Bayesian network meta-analysis to compare the biosimilars to one another.

Similar Effectiveness and Safety Amongst All Bevacizumab Products

In the pairwise analysis, pooling the results of randomized controlled trials (RCTs) comparing bevacizumab biosimilars to the originator in NSCLC, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were not significantly different between groups. Regarding safety, there were no significant differences in grade 3 to 5 adverse events (AEs) between groups. Similarly, for CRC, ORR and incidence of grade 3-5 AEs were not significantly different between biosimilar and reference product groups.

In the Bayesian network meta-analysis, the authors compared each biosimilar with each of the other biosimilars by ranking each one based on its comparison to the reference product. In 7 studies reporting ORR, no significant differences were found between bevacizumab biosimilars for treating NSCLC. In 4 studies reporting PFS and OS, SB8 (Samsung Bioepis), PF-06439535 (Pfizer), MB02 (mAbxience), and FKB238 (Centus Biotherapeutics) showed “clinically equivalent survival benefits,” according to the authors.

No significant differences in the incidence of grade 3 to 5 AEs were detected between any of the treatments. They concluded, “based on the existing evidence, seven biosimilars, including PF-06439535, ABP215, SB8, FKB238, MB02, LY01008 (Luye Pharma), and IBI305 (Innovent Biologics), may have equivalent clinical efficacy and safety to each other in patients with NSCLC by multiple comparisons.”

Data were available on ORR for 3 biosimilars—BE1040V (AryoGen Pharmed), BEVZ92 (mAbxience), and HLX04 (Shanghai Henlius Biotech)— and the originator in patients with CRC. No significant differences between treatments were detected. Two studies on BE1040V and HLX04 reported OS data, and no significant differences were found in the network meta-analysis. Grade 3 to 5 AEs were also comparable. “Hence, BE1040V, BEVZ92, and HLX04 may be equivalent to each other in the population of CRC,” the authors said.

The authors also assessed immunogenicity and found no significant differences between the biologics. They noted that their findings were consistent with those of a previous meta-analysis from 2019 on bevacizumab biosimilars, and wrote that, to their knowledge, theirs is the first Bayesian network meta-analysis to evaluate bevacizumab biosimilars in NSCLC or CRC.

More Data Needed in CRC

Regarding limitations, the authors analyzed only pre-market, phase 3 RCTs, which they said, “have strict inclusion and exclusion criteria and may not truly reflect real-world conditions due to the complexity of clinical patients and settings.” They said that more real-world studies may be needed to validate their findings, as well as more data on bevacizumab biosimilars in CRC, since the evidence in CRC is “still relatively poor, and the treatment regimens used in each trial are not uniform.”


Xu X, Zhang S, Xu T, Zhan M, Chen C, Zhang C. 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. Front Pharmacol. 2022;13:880090. doi:10.3389/fphar.2022.880090

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