Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab

• Published in: BMC cancer Vol. 20; no. 1; pp. 783 - 10
• Main Authors: Alexeev, Sergey M, Khorinko, Andrey V, Mukhametshina, Guzel Z, Shelepen, Konstantin G, Burdaeva, Olga N, Kulik, Sergey A, Satheesh, Chiradoni Thugappa, Srivastava, Kirti, Vikranth, Mummaneni, Kryukov, Fedor, Paltusova, Anastasia N, Shustova, Mariya S, Ivanov, Roman A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20-08-2020; BioMed Central; BMC
• Subjects: Adult; Aged; Angina pectoris; Antibodies; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Area Under Curve; Biological products; Biosimilar Pharmaceuticals - administration & dosage; Biosimilar Pharmaceuticals - adverse effects; Biosimilar Pharmaceuticals - pharmacokinetics; Breast - diagnostic imaging; Breast - pathology; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer metastasis; Cancer therapies; Clinical trials; Dose-Response Relationship, Drug; Double-Blind Method; Double-blind studies; Drug Administration Schedule; Drug dosages; Drug therapy; ErbB-2 protein; Ethics; Female; Gene amplification; Humans; Immunogenicity; Immunotherapy; Laboratories; Medical imaging; Medical research; Metastases; Metastasis; Middle Aged; Monoclonal antibodies; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Patients; Pharmacokinetics; Product development; Radiation therapy; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - metabolism; Response Evaluation Criteria in Solid Tumors; Skin cancer; Statistical analysis; Targeted cancer therapy; Therapeutic Equivalency; Tomography, X-Ray Computed; Toxicity; Trastuzumab; Trastuzumab - administration & dosage; Trastuzumab - adverse effects; Trastuzumab - pharmacokinetics; Young Adult; Russia
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-020-07247-9

BCD-022 is a trastuzumab biosimilar which was shown to be equivalent to reference trastuzumab 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 comparatively assess efficacy and safety of BCD-022 and reference trastuzumab in combination with paclitaxel used as the therapy of metastatic HER2(+) breast cancer. Pharmacokinetics and immunogenicity were also studied.
Patients with no previous treatment for metastatic HER2(+) breast cancer were randomly assigned 1:1 to BCD-022 or reference trastuzumab and were treated with trastuzumab + paclitaxel. Therapy continued for 6 cycles of therapy (every 3 weeks), until progression of the disease or unbearable toxicity. Primary study endpoint was overall response rate. Study goal was to prove equivalent efficacy of BCD-022 and reference trastuzumab. Equivalence margins for 95% CI for difference in overall response rates were set at [- 20%; 20%].
In total 225 patients were enrolled into the study, 115 in BCD-022 arm and 110 in reference trastuzumab arm. Overall response rate was 49.6% in BCD-022 arm and 43.6% in reference trastuzumab arm. Limits of 95% CI for difference of overall response rates between arms were [(- 8.05)-19.89%], thus, they lied within predetermined equivalence margins [- 20%; 20%]. Profile of adverse events was similar between groups (any AEs were reported in 93.81% of patients in BCD-022 arm and 94.55% of patients in reference arm). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding antibody occurrence rate (either BAb or NAb) was found between BCD-022 (n = 3; 2.65%) and comparator (n = 4; 3.64%). Both drug products are characterized with low occurrence rate and short life of anti-trastuzumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures: AUC
, С
, Т
, T
. Analysis of C
did not reveal any significant inter-group differences as well.
Thus, results of this study have demonstrated therapeutic equivalence of trastuzumab biosimilar BCD-022 and referent trastuzumab drug.
The trial was registered with ClinicalTrials.gov (Study Number NCT01764022 ). The date of registration was January 9, 2013.