Email this article Toxicity and safety of the combination of lenvatinib with pembrolizumab in patients with advanced renal cell cancer: The Russian phase IV observational study
- Authors: Volkova M.I.1,2, Kalpinskiy A.S.3, Goncharova O.A.4, Menshikov K.V.5,6, Karabina E.V.7, Dergunov A.S.8, Polshina N.I.9, Alexandrova E.N.10, Lebedinets A.A.11, Panov A.К.12, Sultanbaev A.V.5,6, Usynin E.A.13, Volkonskiy M.V.14, Mikhalyuk V.V.15, Zukov R.A.16,17, Anzhiganova Y.V.16,17, Gusniev M.A.18, Igumnova E.N.19, Kuzmicheva S.V.20, Pokataev I.A.1, Olshanskaya A.S.1, Pervakova N.I.21, Parsadanova E.L.22, Sannikova T.A.23, Bystrov A.A.24, Dubovichenko D.M.25, Miliausha M.R.26, Chubenko V.A.27, Shkret K.A.28, Gorshenina M.N.29, Davlatova M.К.26, Kosareva A.E.30, Lutoshkina O.A.19, Maslova O.A.31, Makhnutina M.V.32, Mishina A.V.33, Murzalina M.Z.34, Podyacheva O.A.35, Kalinin S.A.36,37, Mailyan O.A.3, Safarova A.R.26, Semenova K.O.38, Strokova M.A.39, Urashkina E.Y.38, Shmygina O.S.40
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Affiliations:
- Moscow City Oncological Hospital No. 1 of the Moscow Department of Healthcare
- Russian Medical Academy of Continuous Professional Education
- Hertsen Moscow Oncology Research Institute-branch of the National Medical Research Radiological Centre
- Clinical Oncology Dispensary No. 1
- Republican Clinical Oncology Dispensary
- Bashkir State Medical University
- Tula Regional Clinical Oncologic Dispensary
- Tver Regional Clinical Oncologic Dispensary
- Loginov Moscow Clinical Scientific Center
- Yakutsk Republican Oncologic Dispensary
- Leningrad Regional Clinical Hospital
- Novokuznetsk Branch of Rappoport Kuzbass Clinical Oncologic Dispensary
- Cancer Research Institute - Branch of Tomsk National Research Medical Center
- Moscow City Oncology Hospital No. 62 of the Moscow City Health Department
- Nizhnevartovsk Oncologic Dispensary
- Voino-Yasenetsky Krasnoyarsk State Medical University
- Kryzhanovsky Krasnoyarsk Regional Clinical Oncologic Dispensary
- Republican Oncology Center
- Perm Regional Oncologic Dispensary
- Moscow Regional Oncologic Dispensary
- Rappoport Kuzbass Clinical Oncologic Dispensary
- Sakhalin Regional Oncologic Dispensary
- Perm Regional Hospital
- Moscow City Oncology Hospital No. 62 of the Moscow City Health Department Istra
- Arkhangelsk Clinical Oncologic Dispensary
- SigaI Republican Clinical Oncologic Dispensary of the Ministry of Health of the Republic of Tatarstan
- Napalkov Saint Petersburg Clinical Scientific and Practical Center for Specialised Types of Medical Care (oncological)
- Central City Clinical Hospital No. 24
- Republican Oncologic Dispensary
- Multidisciplinary Clinical Medical Center „Medical City"
- Odintsovo Regional Hospital
- Samara Regional Clinical Oncologic Dispensary
- Sverdlovsk Regional Oncologic Dispensary
- Orenburg Regional Clinical Oncologic Dispensary
- Regional Clinical Oncologic Dispensary
- Pirogov Russian National Research Medical University
- Blokhin National Medical Research Center of Oncology
- Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
- Efetov Crimean Republican Oncologic Clinical Dispensary
- Lotos Medical Center LLC
- Issue: Vol 26, No 1 (2024)
- Pages: 39-47
- Section: Articles
- URL: https://journals.rcsi.science/1815-1434/article/view/258572
- DOI: https://doi.org/10.26442/18151434.2024.1.202629
- ID: 258572
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Abstract
Aim To evaluate the safety and toxicity of lenvatinib with pembrolizumab in unselected patients with advanced renal cell carcinoma (RCC).
Materials and methods. The Russian phase IV observational study included 151 patients with advanced RCC who received lenvatinib with pembrolizumab in a standard dose regimen in 36 clinical centers of the Russian Federation. Most patients were diagnosed with clear cell RCC (n=145, 96.0%), with synchronous (n=77,51.0%) metastasesof more than one location (n=111,73.5%), removed primary tumor (n=98, 64.9%) and were classified into intermediate and poor IMDC prognostic groups (n=111, 73.5%). Median follow-up was 9.6 (1—68) months.
Results. Any adverse events (AEs) were noted in 109 (72.2%), grade ≥3 AEs-in 26 (17.2%), serious AEs-in 9 (6.0%) of 151 patients. There were no deaths caused by AEs. AEs were an indication for lenvatinib dose reduction in 32 (21.2%), a dose interruptions in lenvatinib treatment in 21 (13.9%), and lenvatinib discontinuation in 2 (1.3%) cases. A dose interruptions in pembrolizumab therapy due to AEs was necessary in 15 (9.9%) cases. Both combination drugs were discontinued due to toxicity in 10 (6.6%) cases. AEs were assessed as immune-mediated in 24 (15.9%) patients (grade 3-4 - n=7, 4.6%) and required the prescription of high doses of glucocorticosteroids in 2 (1.3%) patients.
Conclusions. A Russian observational study confirmed the acceptable safety profile of lenvatinib plus pembrolizumab therapy in patients with advanced RCC.
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##article.viewOnOriginalSite##About the authors
Maria I. Volkova
Moscow City Oncological Hospital No. 1 of the Moscow Department of Healthcare; Russian Medical Academy of Continuous Professional Education
Author for correspondence.
Email: mivoLkova@rambler.ru
ORCID iD: 0000-0001-7754-6624
D. Sci. (Med.)
Russian Federation, Moscow; MoscowAlexey S. Kalpinskiy
Hertsen Moscow Oncology Research Institute-branch of the National Medical Research Radiological Centre
Email: dr.kalpinskiy@gmail.com
ORCID iD: 0000-0002-2209-3020
Cand. Sci. (Med.)
Russian Federation, MoscowOlesya A. Goncharova
Clinical Oncology Dispensary No. 1
Email: domosedka81@yandex.ru
ORCID iD: 0000-0002-6322-7144
Department Head, Clinical Oncology Dispensary No. 1.
Russian Federation, KrasnodarKonstantin V. Menshikov
Republican Clinical Oncology Dispensary; Bashkir State Medical University
Email: kmenshikov80@bk.ru
ORCID iD: 0000-0003-3734-2779
Cand. Sci. (Med.)
Russian Federation, Ufa; UfaElena V. Karabina
Tula Regional Clinical Oncologic Dispensary
Email: kev-251@yandex.ru
ORCID iD: 0000-0001-6062-5318
Department Head
Russian Federation, TulaAleksand S. Dergunov
Tver Regional Clinical Oncologic Dispensary
Email: a.dergunov87@yandex.ru
Head of Department
Russian Federation, TverNatalya I. Polshina
Loginov Moscow Clinical Scientific Center
Email: npolshina@yandex.ru
ORCID iD: 0000-0001-5417-0425
oncologist
Russian Federation, MoscowElena N. Alexandrova
Yakutsk Republican Oncologic Dispensary
Email: yarod@gov14.ru
Department Head
Russian Federation, YakutskAndrey A. Lebedinets
Leningrad Regional Clinical Hospital
Email: andrey.lebedinets@yandex.ru
ORCID iD: 0009-0002-0240-6656
Cand. Sci. (Med.), Leningrad Regional Clinical Hospital
Russian Federation, Saint PetersburgAlexey К. Panov
Novokuznetsk Branch of Rappoport Kuzbass Clinical Oncologic Dispensary
Email: donaleksy99@yandex.ru
oncologist
Russian Federation, NovokuznetskAlexander V. Sultanbaev
Republican Clinical Oncology Dispensary; Bashkir State Medical University
Email: sultanbaevav@onkorb.ru
ORCID iD: 0000-0003-0996-5995
Cand. Sci. (Med.)
Russian Federation, Ufa; UfaEvgeny A. Usynin
Cancer Research Institute - Branch of Tomsk National Research Medical Center
Email: gusi70@list.ru
ORCID iD: 0000-0001-7127-0188
D. Sci. (Med.), Cancer Research Institute-Branch of Tomsk National Research Medical Center
Russian Federation, TomskMikhail V. Volkonskiy
Moscow City Oncology Hospital No. 62 of the Moscow City Health Department
Email: mux19@yandex.ru
ORCID iD: 0000-0003-4060-5015
Cand. Sci. (Biol.)
Russian Federation, Istra, KrasnogorskViktorya V. Mikhalyuk
Nizhnevartovsk Oncologic Dispensary
Email: Viktorya-vm@yandex.ru
ORCID iD: 0009-0006-0220-085X
oncologist
Russian Federation, NizhnevartovskRuslan A. Zukov
Voino-Yasenetsky Krasnoyarsk State Medical University; Kryzhanovsky Krasnoyarsk Regional Clinical Oncologic Dispensary
Email: Zukov_rus@mail.ru
ORCID iD: 0000-0003-1576-5930
D. Sci. (Med.), Prof.
Russian Federation, Krasnoyarsk; KrasnoyarskYulia V. Anzhiganova
Voino-Yasenetsky Krasnoyarsk State Medical University; Kryzhanovsky Krasnoyarsk Regional Clinical Oncologic Dispensary
Email: anzhi.yuliya@yandex.ru
ORCID iD: 0000-0002-8388-466X
oncologist
Russian Federation, Krasnoyarsk; KrasnoyarskMagomed A. Gusniev
Republican Oncology Center
Email: m.gusniev@gmail.com
ORCID iD: 0000-0001-9538-8869
oncologist, urologist
Russian Federation, MakhachkalaElena N. Igumnova
Perm Regional Oncologic Dispensary
Email: a02112808m@gmail.com
ORCID iD: 0009-0007-3428-9585
oncologist, Perm Regional Oncologic Dispensary
Russian Federation, PermSvetlana V. Kuzmicheva
Moscow Regional Oncologic Dispensary
Email: mivoLkova@rambler.ru
oncologist, Moscow Regional Oncologic Dispensary
Russian Federation, BalashikhaIlya A. Pokataev
Moscow City Oncological Hospital No. 1 of the Moscow Department of Healthcare
Email: ipokataev@gmail.com
ORCID iD: 0000-0001-9864-3837
D. Sci. (Med.)
Russian Federation, MoscowAnna S. Olshanskaya
Moscow City Oncological Hospital No. 1 of the Moscow Department of Healthcare
Email: ipokataev@gmail.com
ORCID iD: 0000-0003-0389-564X
Cand. Sci. (Med.)
Russian Federation, MoscowNatalia I. Pervakova
Rappoport Kuzbass Clinical Oncologic Dispensary
Email: pni-39@mail.ru
oncologist
Russian Federation, KemerovoElvira L. Parsadanova
Sakhalin Regional Oncologic Dispensary
Email: 2903410@mail.ru
Department Head, Sakhalin Regional Oncologic Dispensary
Russian Federation, Yuzhno-SakhalinskTatyana A. Sannikova
Perm Regional Hospital
Email: doctoron@mail.ru
ORCID iD: 0009-0002-6328-7785
oncologist
Russian Federation, PermAlexandr A. Bystrov
Moscow City Oncology Hospital No. 62 of the Moscow City Health Department Istra
Email: mux19@yandex.ru
Cand. Sci. (Med.)
Russian Federation, KrasnogorskDaria M. Dubovichenko
Arkhangelsk Clinical Oncologic Dispensary
Email: dubovichenko27@yandex.ru
ORCID iD: 0000-0002-1287-0279
Cand. Sci. (Med.)
Russian Federation, ArkhangelskMukhitova R. Miliausha
SigaI Republican Clinical Oncologic Dispensary of the Ministry of Health of the Republic of Tatarstan
Email: Mukhitova.m@gmail.com
ORCID iD: 0000-0002-0741-624X
Cand. Sci. (Med.)
Russian Federation, KazanViacheslav A. Chubenko
Napalkov Saint Petersburg Clinical Scientific and Practical Center for Specialised Types of Medical Care (oncological)
Email: vchubenko@me.com
ORCID iD: 0000-0001-6644-6687
Cand. Sci. (Med.)
Russian Federation, Saint PetersburgKonstantin A. Shkret
Central City Clinical Hospital No. 24
Email: kot_pvl@mail.ru
ORCID iD: 0009-0009-6547-9095
oncologist
Russian Federation, EkaterinburgMariya N. Gorshenina
Republican Oncologic Dispensary
Email: mivoLkova@rambler.ru
Department Head, Republican Oncologic Dispensary
Russian Federation, Yoshkar-OlaMavzhuda К. Davlatova
SigaI Republican Clinical Oncologic Dispensary of the Ministry of Health of the Republic of Tatarstan
Email: dmavzhuda@bk.ru
ORCID iD: 0009-0008-3082-8569
oncologist
Russian Federation, KazanAlina E. Kosareva
Multidisciplinary Clinical Medical Center „Medical City"
Email: 79136786767@yandex.ru
ORCID iD: 0009-0002-6863-247X
Oncologist
Russian Federation, TyumenOlga A. Lutoshkina
Perm Regional Oncologic Dispensary
Email: Lutocomm@yandex.ru
ORCID iD: 0009-0009-9188-7199
clinical pharmacologist
Russian Federation, PermOxana A. Maslova
Odintsovo Regional Hospital
Email: mivoLkova@rambler.ru
oncologist, Department Head, Odintsovo Regional Hospital
Russian Federation, OdintsovoMaria V. Makhnutina
Samara Regional Clinical Oncologic Dispensary
Email: MahnutinaMV@mail.ru
oncologist, Samara Regional Clinical Oncologic Dispensary
Russian Federation, SamaraAnna V. Mishina
Sverdlovsk Regional Oncologic Dispensary
Email: ya.a-nozdrina2016@yandex.ru
ORCID iD: 0009-0002-0311-1817
oncologist
Russian Federation, EkaterinburgMakhabbat Zh. Murzalina
Orenburg Regional Clinical Oncologic Dispensary
Email: tyulegenova88@mail.ru
ORCID iD: 0000-0003-0078-7467
Department Head
Russian Federation, OrenburgOksana A. Podyacheva
Regional Clinical Oncologic Dispensary
Email: doc_ox@mail.ru
Cand. Sci. (Med.), Regional Clinical Oncologic Dispensary
Russian Federation, UlyanovskSergey A. Kalinin
Pirogov Russian National Research Medical University; Blokhin National Medical Research Center of Oncology
Email: hrpc@mail.ru
ORCID iD: 0000-0002-0694-7911
Cand. Sci. (Med.)
Russian Federation, Moscow; MoscowOvsep A. Mailyan
Hertsen Moscow Oncology Research Institute-branch of the National Medical Research Radiological Centre
Email: mivoLkova@rambler.ru
ORCID iD: 0000-0002-9787-8842
Urologist
Russian Federation, MoscowAlfiya R. Safarova
SigaI Republican Clinical Oncologic Dispensary of the Ministry of Health of the Republic of Tatarstan
Email: alfiya70@mail.ru
ORCID iD: 0000-0002-2988-3746
Department Head
Russian Federation, KazanKsenia O. Semenova
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Email: semenowa.xenya2016@yandex.ru
ORCID iD: 0009-0002-0764-7790
oncologist
Russian Federation, ChelyabinskMariya A. Strokova
Efetov Crimean Republican Oncologic Clinical Dispensary
Email: strokovamaria@mail.ru
ORCID iD: 0000-0002-3360-3401
Department Head
Russian Federation, SimferopolEkaterina Yu. Urashkina
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Email: U_Kate_1992@mail.ru
ORCID iD: 0009-0003-5085-5138
oncologist
Russian Federation, ChelyabinskOlesya S. Shmygina
Lotos Medical Center LLC
Email: iva8439@yandex.ru
ORCID iD: 0009-0007-4875-3203
oncologist
Russian Federation, ChelyabinskReferences
- Волкова М.И., Алексеев Б.Я., Гладков О.А., и др. Практические рекомендации по лекарственному лечению почечноклеточного рака. Злокачественные опухоли. 2022;12(3s2-1):579-88 [Volkova MI, Alekseev BIa, Gladkov OA, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu pochechnokletochnogo raka. Malignant Tumours. 2022;12(3s2-1):579-88 (in Russian)]. doi: 10.18027/2224-5057-2022-12-3s2-579-588
- NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer. Version 1.2024 – June 21, 2023. Available at: ef859f09-bbdb-4f93-a071-813955f982bd.pdf (raghavhealthcare.in). Accessed: 15.12.2023.
- Motzer R, Alekseev B, Rha SY, et al; CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021;384(14):1289-300. doi: 10.1056/NEJMoa2035716
- International mRCC Database Consortium. Available at: https://www.imdconline.com/ Accessed: 15.12.2023.
- National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0. 2017. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf. Accessed: 15.12.2023.
- Motzer RJ, Porta C, Eto M, et al. Final prespecified overall survival analysis of CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab vs sunitinib in patients with advanced renal cell carcinoma. ASCO Annual Meeting. Abstract 4502. Presented June 5, 2023.
- Cabanillas ME, Takahashi S. Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer. Semin Oncol. 2019;46(1):57-64. doi: 10.1053/j.seminoncol.2018.11.004
- König D, Läubli H. Mechanisms of Immune-Related Complications in Cancer Patients Treated with Immune Checkpoint Inhibitors. Pharmacology. 2021;106(3-4):123-36. doi: 10.1159/000509081
- Davies M, Duffield EA. Safety of checkpoint inhibitors for cancer treatment: strategies for patient monitoring and management of immune-mediated adverse events. Immunotargets Ther. 2017;6:51-71. doi: 10.2147/ITT.S141577
- De Giglio A, Mezquita L, Auclin E, et al. Impact of Intercurrent Introduction of Steroids on Clinical Outcomes in Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients under Immune-Checkpoint Inhibitors (ICI). Cancers (Basel). 2020;12(10):2827. doi: 10.3390/cancers12102827
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