PMID- 35105329 OWN - NLM STAT- MEDLINE DCOM- 20220307 LR - 20220307 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 22 IP - 1 DP - 2022 Feb 1 TI - Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab. PG - 129 LID - 10.1186/s12885-022-09243-7 [doi] LID - 129 AB - BACKGROUND: 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). METHODS: 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%]. RESULTS: 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(st) and 6(th) study drug injection also demonstrated equivalent PK parameters by all outcome measures. CONCLUSIONS: Thus, the results of this study demonstrated therapeutic equivalence of bevacizumab biosimilar BCD-021 and referent bevacizumab drug. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (Study Number NCT01763645, date of registration 09/01/2013). CI - (c) 2022. The Author(s). FAU - Stroyakovskiy, Daniil L AU - Stroyakovskiy DL AD - Moscow City Oncology Hospital No. 62, Moscow, Russian Federation. FAU - Fadeeva, Natalya V AU - Fadeeva NV AD - Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine, Chelyabinsk, Russian Federation. FAU - Matrosova, Marina P AU - Matrosova MP AD - Nizhny Novgorod Regional Clinical Oncological Dispensary, Nizhny Novgorod, Russian Federation. FAU - Shelepen, Konstantin G AU - Shelepen KG AD - Brest Regional Clinical Cancer Dispensary, Brest, Republic of Belarus. FAU - Adamchuk, Grigoriy A AU - Adamchuk GA AD - Kryviyi Rih Oncology Dispensary, Kryvyi Rih, Ukraine. FAU - Roy, Bodhisatta AU - Roy B AD - Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata, India. FAU - Nagarkar, Rajnish AU - Nagarkar R AD - HCG Manavata Cancer Centre, Nashik, India. FAU - Kalloli, Mahesh AU - Kalloli M AD - KLE Hospital & Research Institute, Belgaum, India. FAU - Zhuravleva, Daria AU - Zhuravleva D AD - JSC BIOCAD, Saint Petersburg, Russian Federation. FAU - Voevodin, Georgiy D AU - Voevodin GD AD - JSC BIOCAD, Saint Petersburg, Russian Federation. FAU - Shustova, Mariya S AU - Shustova MS AD - JSC BIOCAD, Saint Petersburg, Russian Federation. FAU - Kryukov, Fedor AU - Kryukov F AD - JSC BIOCAD, Saint Petersburg, Russian Federation. kryukov@biocad.ru. LA - eng SI - ClinicalTrials.gov/NCT01763645 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20220201 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Biosimilar Pharmaceuticals) RN - 2S9ZZM9Q9V (Bevacizumab) RN - BG3F62OND5 (Carboplatin) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*adverse effects MH - Bevacizumab/*adverse effects MH - Biosimilar Pharmaceuticals/*adverse effects MH - Carboplatin MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Double-Blind Method MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/drug therapy MH - Paclitaxel MH - Russia MH - Therapeutic Equivalency MH - Treatment Outcome MH - Ukraine MH - Young Adult PMC - PMC8808992 COIS- The authors declare that they have no competing interests. EDAT- 2022/02/03 06:00 MHDA- 2022/03/08 06:00 PMCR- 2022/02/01 CRDT- 2022/02/02 05:29 PHST- 2021/07/29 00:00 [received] PHST- 2022/01/24 00:00 [accepted] PHST- 2022/02/02 05:29 [entrez] PHST- 2022/02/03 06:00 [pubmed] PHST- 2022/03/08 06:00 [medline] PHST- 2022/02/01 00:00 [pmc-release] AID - 10.1186/s12885-022-09243-7 [pii] AID - 9243 [pii] AID - 10.1186/s12885-022-09243-7 [doi] PST - epublish SO - BMC Cancer. 2022 Feb 1;22(1):129. doi: 10.1186/s12885-022-09243-7.