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 E.L.1,2, Fedenko A.A.3, Falaleeva N.A.4, Andreeva T.V.5, Afanas'ev S.G.1, Bakaev Z.A.6, Valiev D.I.7, Volkov A.A.8, Kolomiets L.A.1, Krashikhina T.V.9, Miller S.V.1, Mikhaliuk V.V.10, Ogloblin A.N.11, Orlova S.A.12, Pataliak S.V.1, Pokataev I.A.13, Popova N.O.1, Rebrina O.V.5, Safin R.N.14, Stradaeva I.I.15, Trefilova I.V.16, Usol'tseva I.S.17, Usynin E.A.1, Sharov S.V.18, Iukal'chuk D.I.19, Iasieva A.R.13
-
Affiliations:
- Cancer Research Institute – branch of the Tomsk National Research Medical Center of the Russian Academy of Sciences
- Siberian State Medical University
- Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre
- Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Centre
- Smolensk Regional Oncologic Clinical Dispensary
- Khimki Hospital
- City Clinical Hospital No. 8
- PET Technology Center LLC
- Moscow Center for Restorative Treatment LLC
- Nizhnevartovsk Oncologic Dispensary
- Oryol Oncological Dispensary
- Republican Clinical Oncologic Dispensary
- Yudin Moscow City Hospital
- Sigal Republican Clinical Oncological Dispensary
- PET-Technology LLC
- Perm Krai Clinical Hospital
- Sakhalin Regional Oncologic Dispensary
- Clinical Oncologic Dispensary No. 1
- Regional Oncologic Dispensary
- Issue: Vol 26, No 2 (2024)
- Pages: 173-181
- Section: Articles
- URL: https://journals.rcsi.science/1815-1434/article/view/260599
- DOI: https://doi.org/10.26442/18151434.2024.2.202744
- ID: 260599
Cite item
Full Text
Abstract
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.
Full Text
##article.viewOnOriginalSite##About the authors
Evgeny L. Choynzonov
Cancer Research Institute – branch of the Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University
Author for correspondence.
Email: center@tnimc.ru
ORCID iD: 0000-0002-3651-0665
D. Sci. (Med.), Prof., Acad. RAS
Russian Federation, Tomsk; TomskAlexander A. Fedenko
Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre
Email: center@tnimc.ru
ORCID iD: 0000-0003-4927-5585
D. Sci. (Med.), Prof.
Russian Federation, MoscowNatalia A. Falaleeva
Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Centre
Email: center@tnimc.ru
ORCID iD: 0000-0002-0023-4216
D. Sci. (Med.)
Russian Federation, ObninskTatiana V. Andreeva
Smolensk Regional Oncologic Clinical Dispensary
Email: center@tnimc.ru
Department Head
Russian Federation, SmolenskSergei G. Afanas'ev
Cancer Research Institute – branch of the Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: center@tnimc.ru
D. Sci. (Med.), Prof.
Russian Federation, TomskZelimkhan A. Bakaev
Khimki Hospital
Email: center@tnimc.ru
Department Head
Russian Federation, KhimkiDanila I. Valiev
City Clinical Hospital No. 8
Email: center@tnimc.ru
Department Head
Russian Federation, ChelyabinskAleksandr A. Volkov
PET Technology Center LLC
Email: center@tnimc.ru
Chief doctor
Russian Federation, UfaLarisa A. Kolomiets
Cancer Research Institute – branch of the Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: center@tnimc.ru
D. Sci. (Med.), Prof.
Russian Federation, TomskTatiana V. Krashikhina
Moscow Center for Restorative Treatment LLC
Email: center@tnimc.ru
Cand. Sci. (Med.)
Russian Federation, KhimkiSergei V. Miller
Cancer Research Institute – branch of the Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: center@tnimc.ru
D. Sci. (Med.)
Russian Federation, TomskViktoriia V. Mikhaliuk
Nizhnevartovsk Oncologic Dispensary
Email: center@tnimc.ru
Department Head
Russian Federation, NizhnevartovskAndrei N. Ogloblin
Oryol Oncological Dispensary
Email: center@tnimc.ru
Department Head
Russian Federation, OryolSvetlana A. Orlova
Republican Clinical Oncologic Dispensary
Email: center@tnimc.ru
Department Head
Russian Federation, CheboksaryStanislav V. Pataliak
Cancer Research Institute – branch of the Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: center@tnimc.ru
Cand. Sci. (Med.)
Russian Federation, TomskIlya A. Pokataev
Yudin Moscow City Hospital
Email: center@tnimc.ru
ORCID iD: 0000-0001-9864-3837
D. Sci. (Med.)
Russian Federation, MoscowNataliia O. Popova
Cancer Research Institute – branch of the Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: center@tnimc.ru
Cand. Sci. (Med.)
Russian Federation, TomskOlesia V. Rebrina
Smolensk Regional Oncologic Clinical Dispensary
Email: center@tnimc.ru
oncologist
Russian Federation, SmolenskRustem N. Safin
Sigal Republican Clinical Oncological Dispensary
Email: center@tnimc.ru
Department Head
Russian Federation, KazanIrina Iu. Stradaeva
PET-Technology LLC
Email: center@tnimc.ru
Department Head
Russian Federation, BalashikhaIuliia V. Trefilova
Perm Krai Clinical Hospital
Email: center@tnimc.ru
Department Head
Russian Federation, PermInessa S. Usol'tseva
Sakhalin Regional Oncologic Dispensary
Email: center@tnimc.ru
Department Head
Russian Federation, Yuzhno-SakhalinskEvgenii A. Usynin
Cancer Research Institute – branch of the Tomsk National Research Medical Center of the Russian Academy of Sciences
Email: center@tnimc.ru
D. Sci. (Med.)
Russian Federation, TomskSergey V. Sharov
Clinical Oncologic Dispensary No. 1
Email: center@tnimc.ru
ORCID iD: 0000-0002-8715-2992
Cand. Sci. (Med.)
Russian Federation, KrasnodarDenis Iu. Iukal'chuk
Regional Oncologic Dispensary
Email: center@tnimc.ru
Department Head
Russian Federation, IrkutskAishat R. Iasieva
Yudin Moscow City Hospital
Email: center@tnimc.ru
oncologist
Russian Federation, MoscowReferences
- Joshi D, Khursheed R, Gupta S, et al. Biosimilars in oncology: Latest trends and regulatory status. Pharmaceutics. 2022;14(12):2721. doi: 10.3390/pharmaceutics14122721
- Федянин М.Ю., Снеговой А.В., Бредер В.В., и др. Токсичность, ассоциированная с ингибиторами иммунных контрольных точек: анализ иммуноопосредованных нежелательных явлений при применении биоаналога пембролизумаба (Пемброриа). Безопасность и риск фармакотерапии. 2023;11(2):215-30 [Fedyanin MYu, Snegovoy AV, Breder VV, et al. Toxicity associated with immune checkpoint inhibitors: Analysis of immune-related adverse events with a pembrolizumab biosimilar (Pembroria). Safety and Risk of Pharmacotherapy (in Russian)]. doi: 10.30895/2312-7821-2023-11-2-360
- Han Y, Liu D, Li L. PD-1/PD-L1 pathway: Current researches in cancer. Am J Cancer Res. 2020;10(3):727-42. PMID: 32266087
- Лядова М.А., Лядов В.К. Иммуноопосредованные нежелательные явления при терапии ингибиторами контрольных точек иммунитета: обзор литературы. Современная Онкология. 2021;23(2):319-26 [Lyadova MA, Lyadov VK. Immune-mediated adverse events in immune checkpoint inhibitors therapy: Literature review. Journal of Modern Oncology. 2021;23(2):319-26 (in Russian)]. doi: 10.26442/18151434.2021.2.200502
- El Osta B, Hu F, Sadek R, et al. Not all immune-checkpoint inhibitors are created equal: Meta-analysis and systematic review of immune-related adverse events in cancer trials. Crit Rev Oncol Hematol. 2017;119:1-12. doi: 10.1016/j.critrevonc.2017.09.002
- Kwok G, Yau TC, Chiu JW, et al. Pembrolizumab (Keytruda). Hum Vaccin Immunother. 2016;12(11):2777-89. doi: 10.1080/21645515.2016.1199310
- Раскин Г.А., Мухина М.С., Каурцева А.С., и др. Определение микросателлитной нестабильности и состояния генов репарации неспаренных нуклеотидов ДНК при опухолях различных локализаций. Архив патологии. 2023;85(1):36-42 [Raskin GA, Mukhina MS, Kaurtseva AS, et al. Microsatellite instability and DNA mismatch repair deficiency detection in tumors of various sites. Russian Journal of Archive of Pathology. 2023;85(1):36-42 (in Russian)]. doi: 10.17116/patol20238501136
- Jin Z, Shen J, Wang C, et al. Narrative review of pembrolizumab for the treatment of esophageal cancer: Evidence and outlook. Ann Transl Med. 2021;9(14):1189. doi: 10.21037/atm-21-2804
- Allouchery M, Beuvon C, Pérault-Pochat MC, et al. Safety of immune checkpoint inhibitor resumption after interruption for immune-related adverse events, a narrative review. Cancers (Basel). 2022;14(4):955. doi: 10.3390/cancers14040955
- Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf. Accessed: 05.04.2024.
- Kubo T, Hirohashi Y, Tsukahara T, et al. Immunopathological basis of immune-related adverse events induced by immune checkpoint blockade therapy. Immunol Med. 2022;45(2):108-18. doi: 10.1080/25785826.2021.1976942
- Olsen TA, Zhuang TZ, Caulfield S, et al. Advances in knowledge and management of immune-related adverse events in cancer immunotherapy. Front Endocrinol (Lausanne). 2022;13:779915. doi: 10.3389/fendo.2022.779915
- Vaddepally R, Doddamani R, Sodavarapu S, et al. Review of immune-related adverse events (irAEs) in nonsmall-cell lung cancer (NSCLC) – their incidence, management, multi-organ irAEs, and rechallenge. Biomedicines. 2022;10(4):790. doi: 10.3390/biomedicines10040790
- Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: A systematic review and meta-analysis. JAMA Oncol. 2018;4(12):1721-8. doi: 10.1001/jamaoncol.2018.3923
- Shiotsu S, Yoshimura A, Yamada T, et al. Pembrolizumab monotherapy for untreated PD-L1-Positive non-small cell lung cancer in the elderly or those with poor performance status: A prospective observational study. Front Oncol. 2022;12:904644. doi: 10.3389/fonc.2022.904644
- Cavaille F, Peretti M, Garcia ME, et al. Real-world efficacy and safety of pembrolizumab in patients with non-small cell lung cancer: A retrospective observational study. Tumori. 2021;107(1):32-8. doi: 10.1177/0300891620926244
- Pillai RN, Behera M, Owonikoko TK, et al. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature. Cancer. 2018;124(2):271-7. doi: 10.1002/cncr.31043
- Taylor MH, Schmidt EV, Dutcus C, et al. The LEAP program: Lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021;17(6):637-48. doi: 10.2217/fon-2020-0937
- Wu YL, Zhang L, Fan Y, et al. Randomized clinical trial of pembrolizumab vs chemotherapy for previously untreated Chinese patients with PD-L1-positive locally advanced or metastatic non-small-cell lung cancer: KEYNOTE-042 China Study. Int J Cancer. 2021;148(9):2313-20. doi: 10.1002/ijc.33399
- Matsubara N, de Wit R, Balar AV, et al. Pembrolizumab with or without lenvatinib as first-line therapy for patients with advanced urothelial carcinoma (LEAP-011): A phase 3, randomized, double-blind trial. Eur Urol. 2024;85(3):229-38. doi: 10.1016/j.eururo.2023.08.012
- Ksienski D, Wai ES, Croteau N, et al. Pembrolizumab for advanced non-small cell lung cancer: Efficacy and safety in everyday clinical practice. Lung Cancer. 2019;133:110-6. doi: 10.1016/j.lungcan.2019.05.005
- Makker V, Aghajanian C, Cohn AL, et al. A phase IB/II study of lenvatinib and pembrolizumab in advanced endometrial carcinoma (Study 111/KEYNOTE-146): Long-term efficacy and safety update. J Clin Oncol. 2023;41(5):974-9. doi: 10.1200/JCO.22.01021
- McDermott DF, Lee JL, Ziobro M, et al. Open-label, single-arm, phase ii study of pembrolizumab monotherapy as first-line therapy in patients with advanced non-clear cell renal cell carcinoma. J Clin Oncol. 2021;39(9):1029-39. doi: 10.1200/JCO.20.02365