Safety of Pembroria® during non-medical switching from Keytruda® in patients with advanced malignant neoplasms of various localizations: the REFLECTION real-world study
Authors: Choynzonov Evgeny L. , Fedenko Alexander A. , Falaleeva Natalia A. , Andreeva Tatiana V. , Afanas'ev Sergei G. , Bakaev Zelimkhan A. , Valiev Danila I. , Volkov Aleksandr A. , Kolomiets Larisa A. , Krashikhina Tatiana V. , Miller Sergei V. , Mikhaliuk Viktoriia V. , Ogloblin Andrei N. , Orlova Svetlana A. , Pataliak Stanislav V. , Pokataev Ilya A. , Popova Nataliia O. , Rebrina Olesia V. , Safin Rustem N. , Stradaeva Irina Iu. , Trefilova Iuliia V. , Usol'tseva Inessa S. , Usynin Evgenii A. , Sharov Sergey V. , Iukal'chuk Denis Iu. , Iasieva Aishat R. 
Published: July 2024

Background. Post-registration observational studies with switching therapy from the original drug to a biosimilar for non-medical indications allow us to assess the safety and effectiveness of this type of switching in real clinical practice.
Aim. Evaluation of the safety and effectiveness of non-medical switching from the original drug Keytruda® to the biosimilar drug Pembroria® in patients with various oncological pathologies in real clinical practice (REFLECTION).
Materials and methods. A retrospective analysis of data from electronic medical records from 21 medical institutions of the Russian Federation for the period 2020–2023 was carried out. Data were included from patients with cancer of various locations who received at least 2 injections of Keytruda® followed by switching to Pembroria® for non-medical indications (at least 2 injections). Primary criteria: incidence of immune-mediated adverse reactions (ImARs) of any severity. Secondary indicators: incidence of ImARs of various degrees of severity and infusion reactions, frequency of objective response rate (according to RECIST 1.1 criteria).
Results. The analysis included data from 382 patients (male/female 200/182, median age 62 years) with NSCLC (24.1%), RCC (23.3%), melanoma (20.4%) and cancer of other localization. Patients received Keytruda® on 1st and 2nd lines (54.2 and 25.4% of patients, respectively), on 3 or 4 lines (14.1%), or as part of adjuvant therapy (6.3%). 50.5% of patients received pembrolizumab as monotherapy. The median number of administrations was 7.0 and 5.0 for Keytruda® and Pembroria®, respectively. ImARs were registered in 44 (11.5%) patients (60 ImARs), including 40 ImARs in 35 (9.2%) patients while using Keytruda® and 20 ImARs in 17 (2.4%) patients with Pembroria®. The most common ImARs were hypothyroidism, hyperthyroidism, and hepatitis; the frequency of these ImARs was higher with Keytruda® (EAER for hypothyroidism 0.00422 and 0.00144, for hepatitis – 0.00124 and 0.00096, respectively). All 5 reported cases of hyperthyroidism in patients on Keytruda® (EAER 0.00124), were resolved before switching to Pembroria®. No infusion-related reactions or deaths due to ImARs have been reported. The objective response rate was comparable – 104 (32.6%) and 90 (29.2%) patients оn Keytruda® and Pembroria® therapy, respectively. Most patients maintained disease control after switching to Pembroria® [progression was recorded in 29 (9.4%) patients after switching to a biosimilar].
Conclusion. The safety profiles of Keytruda® and Pembroria® were satisfactory and comparable in this study. Switching from therapy with Keytruda® to Pembroria® is not accompanied by an increase in the frequency or severity of ImARs. Switching from Keytruda® to Pembroria® maintains disease control in most patients.