Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab

• Published in: BMC cancer 2022-02, Vol.22 (1), p.129-129, Article 129
• Main Authors: Stroyakovskiy, Daniil L, Fadeeva, Natalya V, Matrosova, Marina P, Shelepen, Konstantin G, Adamchuk, Grigoriy A, Roy, Bodhisatta, Nagarkar, Rajnish, Kalloli, Mahesh, Zhuravleva, Daria, Voevodin, Georgiy D, Shustova, Mariya S, Kryukov, Fedor
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antibodies; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bevacizumab; Bevacizumab - adverse effects; Biological products; Biosimilar pharmaceuticals; Biosimilar Pharmaceuticals - adverse effects; Carboplatin; Carcinoma, Non-Small-Cell Lung - drug therapy; Care and treatment; Chemotherapy; Clinical trials; Comparative analysis; Diagnosis; Double-Blind Method; Double-blind studies; Drug dosages; Ethics; Female; Humans; Lung cancer, Non-small cell; Lung Neoplasms - drug therapy; Male; Medical imaging; Metastasis; Middle Aged; Monoclonal antibodies; Neoplasm Recurrence, Local - drug therapy; Non-small cell lung carcinoma; Paclitaxel; Patients; Pharmacokinetics; Response rates; Russia; Small cell lung carcinoma; Squamous cell carcinoma; Statistical analysis; Targeted cancer therapy; Therapeutic Equivalency; Toxicity; Treatment Outcome; Ukraine; Vascular endothelial growth factor; Young Adult
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-09243-7

BCD-021 is a bevacizumab biosimilar which was shown to be equivalent to reference bevacizumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to compare efficacy and safety of BCD-021 and reference bevacizumab in combination with paclitaxel and carboplatin in a first-line treatment of inoperable or advanced non-squamous non-small-cell lung cancer (NSCLC). Patients with no previous treatment for advanced non-squamous NSCLC were randomly assigned 3:2 to BCD-021 or reference bevacizumab and were treated with bevacizumab + paclitaxel + carboplatin. Therapy continued for 6 cycles (every 3 weeks), until progression of the disease or unbearable toxicity. The primary study endpoint was the overall response rate. The study goal was to prove the equivalent efficacy of BCD-021 and reference bevacizumab. Equivalence margins for 95% CI for the difference in the overall response rates were set at [-18%; 18%], for 90% CI for the ratio of overall response rate were set at [67%; 150%]. In total 357 patients were enrolled in the study, 212 in the BCD-021 group and 145 in the reference bevacizumab group. The ORR was 34.63% in the BCD-022 group and 33.82% in the reference bevacizumab group. Limits of 95% CI for the difference in overall response rates between the groups were [-9.47%; 11.09%]. Limits of 90% CI for the ratio of overall response rate between the groups were [79.6%; 131.73%]. For both approaches CI lied within predetermined equivalence margins. Profile of adverse events (AEs) was similar between the groups (any AEs were reported in 86.89% of patients in BCD-021 group and 89.05% of patients in reference group). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding anti-drug antibody occurrence rate was found between BCD-022 (n=4; 1.96%) and comparator (n=5; 3.65%). Both drug products showed low occurrence rate and short life of anti-bevacizumab antibodies. Pharmacokinetics assessment after 1 and 6 study drug injection also demonstrated equivalent PK parameters by all outcome measures. Thus, the results of this study demonstrated therapeutic equivalence of bevacizumab biosimilar BCD-021 and referent bevacizumab drug. The trial was registered with ClinicalTrials.gov (Study Number NCT01763645, date of registration 09/01/2013).