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Results of an international, double-blind, randomized, phase III clinical trial to compare the efficacy and safety of a biosimilar pertuzumab (BCD-178) with reference pertuzumab in patients with HER2-positive breast cancer

https://doi.org/10.33667/2078-5631-2025-11-7-16

Abstract

Introduction. The increasing need for affordable treatment options for patients with HER2-positive breast cancer necessitates the development of pertuzumab biosimilars to expand access to effective therapies. BCD-178 is a pertuzumab biosimilar that has demonstrated equivalence to reference pertuzumab (RP) based on physicochemical characterization, preclinical in vitro and in vivo and clinical phase I study. The international, multicenter, Phase III clinical trial BCD-178–2/PREFER was conducted to comparatively evaluate the efficacy and safety of BCD-178 and RP in combination with TCHP regimen for neoadjuvant therapy in patients with HER2-positive breast cancer.

Objective. To compare the efficacy and safety of the pertuzumab biosimilar BCD-178 and RP when used in a neoadjuvant setting for patients with HER2-positive breast cancer.

Methods. The study included female patients aged 18–75 years with histologically confirmed invasive HER2-positive breast cancer and the absence of estrogen receptor (ER) and progesterone receptor (PR) expression. Patients were randomized 1:1 to receive either BCD-178 or RP. The primary endpoint was the proportion of patients achieving a total pathological complete response – tpCR (ypT0/is, ypN 0) based on the conclusion of a central independent review after completion of the neoadjuvant therapy phase.

Results. A total of 380 patients were randomized into the study. The proportions of patients achieving tpCR (95 % CI) were not statistically different between the treatment groups (p=0.6521, Cochran–Mantel–Haenszel method). The risk difference (95 % CI) for achieving tpCR between the groups was within the pre-defined equivalence boundaries, demonstrating equivalent efficacy of BCD-178 and RP. The treatment groups were comparable in terms of safety profile, including the incidence of adverse reactions (ARs). The most common (≥10 % of patients) ARs were diarrhea and anemia. The pharmacokinetics and immunogenicity of the drugs were comparable.

Conclusions. The study demonstrated comparability between BCD-178 and RP in terms of efficacy, safety, pharmacokinetics, and immunogenicity when used in the neoadjuvant treatment of patients with HER2-positive ER/PR-negative breast cancer.

About the Authors

L. G. Zhukova
Moscow Clinical Scientific and Practical Center named after A.S. Loginov, Moscow Department of Health
Russian Federation

Zhukova Lyudmila G.

Moscow


E. V. Artamonova
N.N. Blokhin National Medical Investigation Centre of Oncology
Russian Federation

Artamonova Elena V.

Moscow


S. A. Demidova
Minsk City Clinical Oncology Center
Belarus

Demidova Svetlana A.

Minsk


K. D. Penkov
Euromedservice
Russian Federation

Penkov Konstantin D.

St. Petersburg


P. V. Krivorotko
N.N. Petrov National Medical Research Center of Oncology
Russian Federation

Krivorotko Petr V.

Saint Petersburg


O. A. Gladkov
LLC «EVIMED»
Russian Federation

Gladkov Oleg A.

Chelyabinsk


N. V. Kovalenko
Volgograd Regional Clinical Oncology Dispensary
Russian Federation

Kovalenko Nadezhda V.

Volgograd


N. A. Falaleeva
National Medical Research Center of Radiology
Russian Federation

Falaleeva Natalia A.

Obninsk


R. I. Kunafina
Republican Clinical Oncology Dispensary
Russian Federation

Kunafina Regina I.

Ufa


L. Yu. Vladimirova
National Medical Research Center of Oncology
Russian Federation

Vladimirova Lyubov Yu.

Rostov-on-Don


M. A. Lyadova
City Clinical Oncology Hospital No. 1 of the Moscow City Health Department
Russian Federation

Lyadova Marina A.

Moscow


A. S. Mochalova
JSC Group of Companies «Medsi»
Pakistan

Mochalova Anastasia S.

Krasnogorsk


Dr. Munira Moosajee
Aga Khan University Hospital
Pakistan

Dr. Munira Moosajee

Karachi


A. V. Zimina
Clinical Oncology Dispensary
Russian Federation

Zimina Anastasia V.

Omsk


S. V. Ogorodnikova
JSC North-West Center for Evidence- Based Medicine
Russian Federation

Ogorodnikova Svetlana V.

St. Petersburg


D. V. Kirtbaya
Oncology Dispensary No. 2
Russian Federation

Kirtbaya Dmitry V.

Sochi


Dr. Adnan Abdul Jabbar
Dr. Ziauddin Hospital
Pakistan

Dr. Adnan Abdul Jabbar

Karachi


N. V. Fadeeva
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine, Oncology Dept of Antitumor Drug Therapy
Russian Federation

Fadeeva Natalia V.

Chelyabinsk


I. S. Shumskaya
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation

Shumskaya Irina S.

Nizhny Novgorod


T. T. Agishev
Clinical Hospital of the Russian Academy of Sciences
Russian Federation

Agishev Timur T.

St. Petersburg


I. A. Koroleva
Reaviz Medical University
Russian Federation

Koroleva Irina A.

Samara


V. M. Moiseenko
Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
Russian Federation

Moiseenko Vladimir M.

S. Petersburg


D. L. Stroyakovsky
Moscow City Oncology Hospital No. 62, Moscow City Health Department
Russian Federation

Stroyakovsky Daniil L.

Moscow


S. V. Khokhlova
National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov
Russian Federation

Khokhlova Svetlana V.

Moscow


I. O. Belogortsev
Leningrad Regional Clinical Oncology Dispensary named after L.D. Roman
Russian Federation

Belogortsev Igor O.

St. Petersburg


D. A. Tantsyrev
Altai Regional Oncology Dispensary
Russian Federation

Tantsyrev Denis A.

Barnaul


V. N. Belyakovsky
Gomel Regional Clinical Oncology Dispensary
Belarus

Belyakovsky Vasily

N.Gomel


A. Sh. Pirmagomedov
LLC «Novaya Liniya»
Russian Federation

Pirmagomedov Albert Sh.

Nalchik


V. V. Kozlov
Novosibirsk Regional Clinical Oncology Dispensary
Russian Federation

Kozlov Vadim V.

Novosibirsk


N. B. Ermakov
Republican Scientific and Practical Center of Oncology and Medical Radiology named after N.N. Alexandrov
Belarus

Ermakov Nikolay B.

Minsk


A. L. Obukhov
Vitebsk Regional Clinical Oncology Dispensary
Belarus

Obukhov Alexey L.

Vitebsk


S. V. Odintsova
JSC «Modern Medical Technologies»
Russian Federation

Odintsova Svetlana V.

St. Petersburg


N. V. Kislov
Regional Clinical Oncology Hospital
Russian Federation

Kislov Nikolay V.

Yaroslavl


S. Yu. Sletina
LLC «Vitamed»
Russian Federation

Sletina Svetlana Y.

Moscow


S. Z. Safina
Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M.Z. Sigala
Russian Federation

Safina Sufiya Z.

Kazan


Ya. S. Chapko
Arkhangelsk Clinical Oncology Dispensary
Russian Federation

Chapko Yana S.

Arkhangelsk


N. E. Musaeva
Krasnoyarsk Regional Oncology Dispensary named after A.I. Kryzhanovsky
Russian Federation

Musaeva Natalya E.

Krasnoyarsk


V. M. Unguryan
Kostroma Oncology Dispensary
Russian Federation

Unguryan Vladimir M.

Kostroma


S. V. Orlov
LLC «EuroCityClinic»
Russian Federation

Orlov Sergey V.

St. Petersburg


I. A. Rozhkova
Kaluga Regional Clinical Oncology Dispensary
Russian Federation

Rozhkova Irina A.

Kaluga


P. I. Skopin
National Research Mordovian State University named after N.P. Ogarev
Russian Federation

Skopin Pavel I.

Saransk


Dr. Qasim M Buttar
Shaheed Zulfiqar Ali Bhutto Medical University
Pakistan

Dr. Qasim M Buttar

Islamabad


O. A. Goncharova
Clinical Oncology Dispensary No. 1
Russian Federation

Goncharova Olesya A.

Krasnodar


E. G. Topuzov
I.I. Mechnikov North-West State Medical University
Russian Federation

Topuzov Eskender G.

St. Petersburg


V. S. Volkov
Brest Regional Oncology Dispensary
Belarus

Volkov Vitaly S.

Brest


N. V. Ivanova
Mogilev Regional Oncology Dispensary
Belarus

Ivanova Natalya V.

Mogilev


D. P. Norik
Grodno University Clinic
Belarus

Norik Dmitry P.

Grodno


M. Yu. Fedyanin
Moscow Multidisciplinary Clinical Center «Kommunarka» of the Moscow City Health Department; National Medical and Surgical Center named after N.I. Pirogov
Russian Federation

Fedyanin Mikhail Yu.

Moscow


I. V. Karnaukhov
Saint Petersburg State University, Clinic of High Medical Technologies named after N.I. Pirogov
Russian Federation

Karnaukhov Ivan V.

St. Petersburg


A. V. Sobolev
Kuzbass Clinical Oncology Dispensary named after M.S. Rappoport
Russian Federation

Sobolev Alexander V.

Kemerovo


T. T. Andabekov
LLC «AV Medical Group»
Russian Federation

Andabaykov Timur T.

St. Petersburg


Dr. Azhar Shafi
Shifa International Hospital
Pakistan

Dr. Azhar Shafi

Islamabad


N. N. Lozovaya
LLC «Ars Medica Center»
Russian Federation

Lozovaya Natalia N.

Kaliningrad


I. V. Sorokina
JSC «Biocad»
Russian Federation

Sorokina Irina V.

St. Petersburg


Yu. N. Linkova
JSC «Biocad»
Russian Federation

Linkova Yulia N.

St. Petersburg


A. V. Zinkina-Orikhan
JSC «Biocad»
Russian Federation

Zinkina-Orikhan Arina V.

St. Petersburg


V. S. Chistyakov
JSC «Biocad»
Russian Federation

Chistyakov Vladimir S.

St. Petersburg


A. A. Lutsky
JSC «Biocad»
Russian Federation

Lutsky Anton A.

St. Petersburg


A. A. Porozova
JSC «Biocad»
Russian Federation

Porozova Anastasia A.

St. Petersburg


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Review

For citations:

Zhukova L.G., Artamonova E.V., Demidova S.A., Penkov K.D., Krivorotko P.V., Gladkov O.A., Kovalenko N.V., Falaleeva N.A., Kunafina R.I., Vladimirova L.Yu., Lyadova M.A., Mochalova A.S., Moosajee D., Zimina A.V., Ogorodnikova S.V., Kirtbaya D.V., Jabbar D., Fadeeva N.V., Shumskaya I.S., Agishev T.T., Koroleva I.A., Moiseenko V.M., Stroyakovsky D.L., Khokhlova S.V., Belogortsev I.O., Tantsyrev D.A., Belyakovsky V.N., Pirmagomedov A.Sh., Kozlov V.V., Ermakov N.B., Obukhov A.L., Odintsova S.V., Kislov N.V., Sletina S.Yu., Safina S.Z., Chapko Ya.S., Musaeva N.E., Unguryan V.M., Orlov S.V., Rozhkova I.A., Skopin P.I., Buttar D., Goncharova O.A., Topuzov E.G., Volkov V.S., Ivanova N.V., Norik D.P., Fedyanin M.Yu., Karnaukhov I.V., Sobolev A.V., Andabekov T.T., Shafi D., Lozovaya N.N., Sorokina I.V., Linkova Yu.N., Zinkina-Orikhan A.V., Chistyakov V.S., Lutsky A.A., Porozova A.A. Results of an international, double-blind, randomized, phase III clinical trial to compare the efficacy and safety of a biosimilar pertuzumab (BCD-178) with reference pertuzumab in patients with HER2-positive breast cancer. Medical alphabet. 2025;(11):7-16. (In Russ.) https://doi.org/10.33667/2078-5631-2025-11-7-16

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ISSN 2078-5631 (Print)
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