Email this article Real-world efficacy and safety of lenvatinib plus pembrolizumab in advanced renal cell carcinoma: Updated data from a Russian observational study
- Authors: Volkova M.I.1,2, Kalpinskiy A.S.3, Goncharova O.A.4, Menshikov K.V.5,6, Stativko O.A.1, Karabina E.V.7, Dergunov A.S.8, Polshina N.I.9, Alexandrova E.N.10, Lebedinets A.A.11, Panov A.K.12, Sultanbaev A.V.5,13, Usynin E.A.14, Volkonskiy M.V.15, Mikhalyuk V.V.16, Zukov R.A.17,18, Anzhiganova Y.V.17,18, Gusniev M.A.19, Igumnova E.N.20, Kuzmicheva S.V.21, Pokataev I.A.1, Olshanskaya A.S.1, Pervakova N.I.22, Parsadanova E.L.23, Sannikova T.A.24, Bystrov A.A.15, Dubovichenko D.M.25, Mukhitova M.R.26, Chubenko V.A.27, Shkret K.A.28, Gorshenina M.N.29, Semenov A.V.30, Davlatova M.K.26, Kosareva A.E.31, Lutoshkina O.A.20, Maslova O.A.21, Tarasova A.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
-
Affiliations:
- Moscow State Budgetary Healthcare Institution "Oncological Center No. 1 of Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department"
- 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, Krasnodar
- Republican Clinical Oncology Dispensary, Ufa
- 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
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences
- 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, Makhachkala
- Perm Regional Oncologic Dispensary
- Moscow Regional Oncologic Dispensary
- Rappoport Kuzbass Clinical Oncologic Dispensary
- Sakhalin Regional Oncologic Dispensary
- Perm Regional Clinical Hospital
- Arkhangelsk Clinical Oncologic Dispensary
- Sigal 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, Ekaterinburg
- Republican Oncologic Dispensary, Yoshkar-Ola
- Ivanovo Regional Oncology Hospital
- Multidisciplinary Clinical Medical Center „Medical City“
- Samara Regional Clinical Oncologic Dispensary
- Sverdlovsk Regional Oncologic Dispensary
- Orenburg Regional Clinical Oncologic Dispensary
- Regional Clinical Oncologic Dispensary, Ulyanovsk
- Blokhin National Medical Research Center of Oncology
- Pirogov Russian National Research Medical University (Pirogov University)
- Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
- Efetov Crimean Republican Oncologic Clinical Dispensary
- Lotos Medical Center LLC
- Issue: Vol 27, No 3 (2025)
- Pages: 275-283
- Section: Articles
- URL: https://journals.rcsi.science/1815-1434/article/view/363028
- DOI: https://doi.org/10.26442/18151434.2025.3.203443
- ID: 363028
Cite item
Full Text
Abstract
Background. A Russian phase IV observational study was initiated to evaluate the efficacy and safety of lenvatinib with pembrolizumab (Len-Pembro) in patients with advanced renal cell carcinoma (RCC) receiving therapy in real-world practice. This article is based on the results of the third analysis conducted with a median follow-up of 23.1 months and reflects data on the efficacy and safety of Len-Pembro in Russian patients.
Aim. To evaluate the real-world efficacy and safety of Len-Pembro in patients with advanced RCC with a median follow-up increased to 23.1 months. The primary outcome of the study was progression-free survival (PFS), the secondary outcomes included overall survival (OS), progression-free survival on next-line therapy (PFS2), objective response rate (ORR), duration of response, as well as safety.
Materials and methods. The study included data from 165 patients with verified advanced RCC who received Len-Pembro at 36 centers in the Russian Federation from February 05, 2018 to July 30, 2025. The median age was 60 (20–76) years, and 70.3% of the participants were male. Most patients (74.6%) presented with Karnofsky performance score of ≥80%, metachronous metastases (50.9%) of clear cell RCC (93.3%) in >1 organ (75.2%), and had not received any anticancer treatment (91.0%). The IMDC favorable prognosis group included 40 (24.2%), intermediate – 92 (55.8%), and unfavorable prognosis – 33 (20.0%) patients. The median follow-up reached 23.1 (0.5–72.9) months. A total of 110 (66.7%) patients completed Len-Pembro therapy, and 51 (30.9%) patients received next-line treatment.
Results. Median PFS reached 25.8 (95% confidence interval – CI 17.0–34.5) months, 23-month PFS – 52.6%; median OS was 39.9 (95% CI 26.9–52.8) months, 23-month OS – 73.1%; median PFS2 was 33.2 (95% CI 23.4–41.1) months, 23-month PFS2 – 66.9%. The ORR was 49.1%, including 3.0% of complete responses, and the disease control rate was 89.1%. The median duration of response reached 29.7 (95% CI 24.9–34.6) months. The incidence of any adverse events (AEs) was 78.8%, severe AEs occurred in 29.1%, fatal AES – in 1.2%, immune-related AEs – 17.0%, severe immune-related AEs – 6.7%.
Conclusion. In real-world practice, with increased follow-up duration, the values of PFS, OS, and PFS2 were comparable to those obtained in the registrational study, with a lower ORR and a satisfactory safety profile of the combination of Len-Pembro in advanced RCC.
About the authors
Maria I. Volkova
Moscow State Budgetary Healthcare Institution "Oncological Center No. 1 of Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department"; Russian Medical Academy of Continuous Professional Education
Author for correspondence.
Email: mivolkova6@gmail.com
ORCID iD: 0000-0001-7754-6624
D. Sci. (Med.), Moscow State Budgetary Healthcare Institution "Oncological Center No. 1"
Russian Federation, Moscow; MoscowAlexey S. Kalpinskiy
Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre
Email: mivolkova6@gmail.com
ORCID iD: 0000-0002-2209-3020
SPIN-code: 7253-9356
Cand. Sci. (Med.)
Russian Federation, MoscowOlesya A. Goncharova
Clinical Oncology Dispensary No. 1, Krasnodar
Email: mivolkova6@gmail.com
ORCID iD: 0000-0002-6322-7144
Department Head
Russian Federation, KrasnodarKonstantin V. Menshikov
Republican Clinical Oncology Dispensary, Ufa; Bashkir State Medical University
Email: mivolkova6@gmail.com
ORCID iD: 0000-0003-3734-2779
Cand. Sci. (Med.)
Russian Federation, Ufa; UfaOlesia A. Stativko
Moscow State Budgetary Healthcare Institution "Oncological Center No. 1 of Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department"
Email: mivolkova6@gmail.com
ORCID iD: 0009-0002-1084-1551
Cand. Sci. (Med.), Moscow State Budgetary Healthcare Institution "Oncological Center No. 1
Russian Federation, MoscowElena V. Karabina
Tula Regional Clinical Oncologic Dispensary
Email: mivolkova6@gmail.com
ORCID iD: 0000-0001-6062-5318
Department Head
Russian Federation, TulaAleksandr S. Dergunov
Tver Regional Clinical Oncologic Dispensary
Email: mivolkova6@gmail.com
Head of Department
Russian Federation, TverNatalya I. Polshina
Loginov Moscow Clinical Scientific Center
Email: mivolkova6@gmail.com
ORCID iD: 0000-0001-5417-0425
Oncologist
Russian Federation, MoscowElena N. Alexandrova
Yakutsk Republican Oncologic Dispensary
Email: mivolkova6@gmail.com
Department Head
Russian Federation, YakutskAndrey A. Lebedinets
Leningrad Regional Clinical Hospital
Email: mivolkova6@gmail.com
ORCID iD: 0009-0002-0240-6656
Cand. Sci. (Med.)
Russian Federation, Saint PetersburgAlexey K. Panov
Novokuznetsk Branch of Rappoport Kuzbass Clinical Oncologic Dispensary
Email: mivolkova6@gmail.com
Oncologist
Russian Federation, NovokuznetskAlexander V. Sultanbaev
Republican Clinical Oncology Dispensary, Ufa; Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences
Email: mivolkova6@gmail.com
ORCID iD: 0000-0003-0996-5995
Cand. Sci. (Med.)
Russian Federation, Ufa; EkaterinburgEvgeny A. Usynin
Tomsk National Research Medical Center
Email: mivolkova6@gmail.com
ORCID iD: 0000-0001-7127-0188
SPIN-code: 1804-0292
D. Sci. (Med.), Cancer Research Institute
Russian Federation, TomskMikhail V. Volkonskiy
Moscow City Oncology Hospital No. 62 of the Moscow City Health Department
Email: mivolkova6@gmail.com
ORCID iD: 0000-0003-4060-5015
Cand. Sci. (Biol.)
Russian Federation, Istra, KrasnogorskViktorya V. Mikhalyuk
Nizhnevartovsk Oncologic Dispensary
Email: mivolkova6@gmail.com
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: mivolkova6@gmail.com
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: mivolkova6@gmail.com
ORCID iD: 0000-0002-8388-466X
Аssistant
Russian Federation, Krasnoyarsk; KrasnoyarskMagomed A. Gusniev
Republican Oncology Center, Makhachkala
Email: mivolkova6@gmail.com
ORCID iD: 0000-0001-9538-8869
Oncologist, urologist
Russian Federation, MakhachkalaElena N. Igumnova
Perm Regional Oncologic Dispensary
Email: mivolkova6@gmail.com
ORCID iD: 0009-0007-3428-9585
Oncologist
Russian Federation, PermSvetlana V. Kuzmicheva
Moscow Regional Oncologic Dispensary
Email: mivolkova6@gmail.com
Oncologist
Russian Federation, BalashikhaIlya A. Pokataev
Moscow State Budgetary Healthcare Institution "Oncological Center No. 1 of Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department"
Email: mivolkova6@gmail.com
ORCID iD: 0000-0001-9864-3837
D. Sci. (Med.), Moscow State Budgetary Healthcare Institution "Oncological Center No. 1"
Russian Federation, MoscowAnna S. Olshanskaya
Moscow State Budgetary Healthcare Institution "Oncological Center No. 1 of Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department"
Email: mivolkova6@gmail.com
ORCID iD: 0000-0003-0389-564X
Cand. Sci. (Med.), Moscow State Budgetary Healthcare Institution "Oncological Center No. 1"
Russian Federation, MoscowNatalia I. Pervakova
Rappoport Kuzbass Clinical Oncologic Dispensary
Email: mivolkova6@gmail.com
Oncologist
Russian Federation, KemerovoElvira L. Parsadanova
Sakhalin Regional Oncologic Dispensary
Email: mivolkova6@gmail.com
Department Head
Russian Federation, Yuzhno-SakhalinskTatyana A. Sannikova
Perm Regional Clinical Hospital
Email: mivolkova6@gmail.com
Oncologist
Russian Federation, PermAlexandr A. Bystrov
Moscow City Oncology Hospital No. 62 of the Moscow City Health Department
Email: mivolkova6@gmail.com
Cand. Sci. (Med.)
Russian Federation, Istra, KrasnogorskDaria M. Dubovichenko
Arkhangelsk Clinical Oncologic Dispensary
Email: mivolkova6@gmail.com
ORCID iD: 0000-0002-1287-0279
Cand. Sci. (Med.)
Russian Federation, ArkhangelskMiliausha R. Mukhitova
Sigal Republican Clinical Oncologic Dispensary of the Ministry of Health of the Republic of Tatarstan
Email: mivolkova6@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: mivolkova6@gmail.com
ORCID iD: 0000-0001-6644-6687
Cand. Sci. (Med.)
Russian Federation, Saint PetersburgKonstantin A. Shkret
Central City Clinical Hospital No. 24, Ekaterinburg
Email: mivolkova6@gmail.com
ORCID iD: 0009-0009-6547-9095
Oncologist
Russian Federation, EkaterinburgMariya N. Gorshenina
Republican Oncologic Dispensary, Yoshkar-Ola
Email: mivolkova6@gmail.com
Department Head
Russian Federation, Yoshkar-OlaAndrey V. Semenov
Ivanovo Regional Oncology Hospital
Email: mivolkova6@gmail.com
D. Sci. (Med.)
Russian Federation, IvanovoMavzhuda K. Davlatova
Sigal Republican Clinical Oncologic Dispensary of the Ministry of Health of the Republic of Tatarstan
Email: mivolkova6@gmail.com
ORCID iD: 0009-0008-3082-8569
Oncologist
Russian Federation, KazanAlina E. Kosareva
Multidisciplinary Clinical Medical Center „Medical City“
Email: mivolkova6@gmail.com
ORCID iD: 0009-0002-6863-247X
Oncologist
Russian Federation, TyumenOlga A. Lutoshkina
Perm Regional Oncologic Dispensary
Email: mivolkova6@gmail.com
ORCID iD: 0009-0009-9188-7199
Clinical pharmacologist
Russian Federation, PermOxana A. Maslova
Moscow Regional Oncologic Dispensary
Email: mivolkova6@gmail.com
Department Head
Russian Federation, BalashikhaAnna V. Tarasova
Samara Regional Clinical Oncologic Dispensary
Email: mivolkova6@gmail.com
Department Head
Russian Federation, SamaraAnna V. Mishina
Sverdlovsk Regional Oncologic Dispensary
Email: mivolkova6@gmail.com
ORCID iD: 0009-0002-0311-1817
Oncologist
Russian Federation, EkaterinburgMakhabbat Zh. Murzalina
Orenburg Regional Clinical Oncologic Dispensary
Email: mivolkova6@gmail.com
ORCID iD: 0000-0003-0078-7467
Department Head
Russian Federation, OrenburgOksana A. Podyacheva
Regional Clinical Oncologic Dispensary, Ulyanovsk
Email: mivolkova6@gmail.com
Cand. Sci. (Med.)
Russian Federation, UlyanovskSergey A. Kalinin
Blokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical University (Pirogov University)
Email: mivolkova6@gmail.com
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: mivolkova6@gmail.com
ORCID iD: 0000-0002-9787-8842
Urologist
Russian Federation, MoscowAlfiya R. Safarova
Sigal Republican Clinical Oncologic Dispensary of the Ministry of Health of the Republic of Tatarstan
Email: mivolkova6@gmail.com
ORCID iD: 0000-0002-2988-3746
Department Head
Russian Federation, KazanKsenia O. Semenova
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Email: mivolkova6@gmail.com
ORCID iD: 0009-0002-0764-7790
Oncologist
Russian Federation, ChelyabinskMariya A. Strokova
Efetov Crimean Republican Oncologic Clinical Dispensary
Email: mivolkova6@gmail.com
ORCID iD: 0000-0002-3360-3401
Department Head
Russian Federation, SimferopolEkaterina Y. Urashkina
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Email: mivolkova6@gmail.com
ORCID iD: 0009-0003-5085-5138
Oncologist
Russian Federation, ChelyabinskOlesya S. Shmygina
Lotos Medical Center LLC
Email: mivolkova6@gmail.com
ORCID iD: 0009-0007-4875-3203
Oncologist
Russian Federation, ChelyabinskReferences
- Волкова М.И., Носов Д.А., Алексеев Б.Я., и др. Практические рекомендации по лекарственному лечению почечноклеточного рака. Практические рекомендации RUSSCO, часть 1. Злокачественные опухоли. 2022;12(3s2-1): 579-88 [Volkova MI, Nosov DA, Alekseev BIa, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu pochechnokletochnogo raka. Prakticheskie rekomendatsii RUSSCO, chast' 1. Malignant Tumours. 2022;12(3s2-1):579-88 (in Russian)]. doi: 10.18027/2224-5057-2022-12-3s2-579-588
- Motzer RJ, Jonasch E, Agarwal N, et al. NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer, v. 1.2025. July 1, 2024.
- Motzer R, Alekseev B, Rha SY, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 2021;384(14):1289-300. doi: 10.1056/NEJMoa2035716
- Motzer RJ, Porta C, Eto M, et al. Lenvatinib plus pembrolizumab versus sunitinib in first-line treatment of advanced renal cell carcinoma: Final prespecified overall survival analysis of CLEAR, a phase III study. J Clin Oncol. 2024;42(11):1222-8. doi: 10.1200/JCO.23.01569
- Albiges L, Gurney H, Atduev V, et al. Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): A single-arm, multicentre, phase 2 trial. Lancet Oncol. 2023;24(8):881-91. doi: 10.1016/S1470-2045(23)00276-0
- Voss M, Gurney H, Atduev V, et al. ASCO GU 2024: First-line pembrolizumab plus lenvatinib for non-clear cell RCC: Extended follow-up of the phase 2 KEYNOTE-B61 study. J Clin Oncol. 2024;42(Suppl. 4):2. doi: 10.1200/jco.2024.42.4_suppl.2
- Волкова М.И., Калпинский А.С., Гончарова О.А., и др. Токсичность и безопасность комбинации ленватиниба с пембролизумабом у больных распространенным почечноклеточным раком. Современная онкология. 2024;26(1):39-47 [Volkova MI, Kalpinskiy AS, Goncharova OA, et al. Toxicity and safety of the combination of lenvatinib with pembrolizumab in patients with advanced renal cell cancer: The Russian phase IV observational study. Journal of Modern Oncology. 2024;26(1): 39-47 (in Russian)]. doi: 10.26442/18151434.2024.1.202629
- Волкова М.И., Калпинский А.С., Гончарова О.А., и др. Эффективность комбинации ленватиниба с пембролизумабом у больных распространенным почечно-клеточным раком. Онкоурология. 2024;20(3):33-48 [Volkova MI, Kalpinskiy AS, Goncharova OA, et al. Efficacy of the combination of lenvatinib with pembrolizumab in patients with advanced renal cell carcinoma. Onkourologiya = Cancer Urology. 2024;20(3):38-48 (in Russian)]. doi: 10.17650/1726-9776-2024-20-3-33-48
- Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026
- Freites-Martinez A, Santana N, Arias-Santiago S, Viera A. Using the Common Terminology Criteria for Adverse Events (CTCAE – Version 5.0) to evaluate the severity of adverse events of anticancer therapies. CTCAE versión 5.0. Evaluación de la gravedad de los eventos adversos dermatológicos de las terapias antineoplásicas. Actas Dermosifiliogr (Engl Ed). 2021;112(1):90-2. doi: 10.1016/j.ad.2019.05.009
- Albiges L, Gurney H, Lee JL, et al. Pembrolizumab plus lenvatinib for previously untreated advanced non-clear cell renal cell carcinoma: 3-Year follow-up of the phase 2 KEYNOTE-B61 study. Presented at the 2025 Kidney Cancer Research Summit; July 17–18, 2025; Boston, MA. Abstract 1.
- Grünwald V, Powles T, Kopyltsov E, et al. Survival by depth of response and efficacy by international metastatic renal cell carcinoma database consortium subgroup with lenvatinib plus pembrolizumab versus sunitinib in advanced renal cell carcinoma: Analysis of the phase 3 randomized CLEAR study. Eur Urol Oncol. 2023;6(4):437-46. doi: 10.1016/j.euo.2023.01.010
- Voss MH, Powles T, McGregor B, et al. Impact of subsequent therapies in patients with advanced renal cell carcinoma receiving lenvatinib plus pembrolizumab or sunitinib in the CLEAR study. Presented at IKCS North America 2022. November 4–5, 2022. Abstract 36.
Supplementary files
