Toxicity and safety of the combination of lenvatinib with pembrolizumab in patients with advanced renal cell cancer: The Russian phase IV observational study

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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.

作者简介

Maria Volkova

Moscow City Oncological Hospital No. 1 of the Moscow Department of Healthcare; Russian Medical Academy of Continuous Professional Education

编辑信件的主要联系方式.
Email: mivoLkova@rambler.ru
ORCID iD: 0000-0001-7754-6624

D. Sci. (Med.)

俄罗斯联邦, Moscow; Moscow

Alexey 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.)

俄罗斯联邦, Moscow

Olesya Goncharova

Clinical Oncology Dispensary No. 1

Email: domosedka81@yandex.ru
ORCID iD: 0000-0002-6322-7144

Department Head, Clinical Oncology Dispensary No. 1.

俄罗斯联邦, Krasnodar

Konstantin Menshikov

Republican Clinical Oncology Dispensary; Bashkir State Medical University

Email: kmenshikov80@bk.ru
ORCID iD: 0000-0003-3734-2779

Cand. Sci. (Med.)

俄罗斯联邦, Ufa; Ufa

Elena Karabina

Tula Regional Clinical Oncologic Dispensary

Email: kev-251@yandex.ru
ORCID iD: 0000-0001-6062-5318

Department Head

俄罗斯联邦, Tula

Aleksand Dergunov

Tver Regional Clinical Oncologic Dispensary

Email: a.dergunov87@yandex.ru

Head of Department

俄罗斯联邦, Tver

Natalya Polshina

Loginov Moscow Clinical Scientific Center

Email: npolshina@yandex.ru
ORCID iD: 0000-0001-5417-0425

oncologist

俄罗斯联邦, Moscow

Elena Alexandrova

Yakutsk Republican Oncologic Dispensary

Email: yarod@gov14.ru

Department Head

俄罗斯联邦, Yakutsk

Andrey Lebedinets

Leningrad Regional Clinical Hospital

Email: andrey.lebedinets@yandex.ru
ORCID iD: 0009-0002-0240-6656

Cand. Sci. (Med.), Leningrad Regional Clinical Hospital

俄罗斯联邦, Saint Petersburg

Alexey Panov

Novokuznetsk Branch of Rappoport Kuzbass Clinical Oncologic Dispensary

Email: donaleksy99@yandex.ru

oncologist

俄罗斯联邦, Novokuznetsk

Alexander Sultanbaev

Republican Clinical Oncology Dispensary; Bashkir State Medical University

Email: sultanbaevav@onkorb.ru
ORCID iD: 0000-0003-0996-5995

Cand. Sci. (Med.)

俄罗斯联邦, Ufa; Ufa

Evgeny 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

俄罗斯联邦, Tomsk

Mikhail 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.)

俄罗斯联邦, Istra, Krasnogorsk

Viktorya Mikhalyuk

Nizhnevartovsk Oncologic Dispensary

Email: Viktorya-vm@yandex.ru
ORCID iD: 0009-0006-0220-085X

oncologist

俄罗斯联邦, Nizhnevartovsk

Ruslan 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.

俄罗斯联邦, Krasnoyarsk; Krasnoyarsk

Yulia 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

俄罗斯联邦, Krasnoyarsk; Krasnoyarsk

Magomed Gusniev

Republican Oncology Center

Email: m.gusniev@gmail.com
ORCID iD: 0000-0001-9538-8869

oncologist, urologist

俄罗斯联邦, Makhachkala

Elena Igumnova

Perm Regional Oncologic Dispensary

Email: a02112808m@gmail.com
ORCID iD: 0009-0007-3428-9585

oncologist, Perm Regional Oncologic Dispensary

俄罗斯联邦, Perm

Svetlana Kuzmicheva

Moscow Regional Oncologic Dispensary

Email: mivoLkova@rambler.ru

oncologist, Moscow Regional Oncologic Dispensary

俄罗斯联邦, Balashikha

Ilya 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.)

俄罗斯联邦, Moscow

Anna 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.)

俄罗斯联邦, Moscow

Natalia Pervakova

Rappoport Kuzbass Clinical Oncologic Dispensary

Email: pni-39@mail.ru

oncologist

俄罗斯联邦, Kemerovo

Elvira Parsadanova

Sakhalin Regional Oncologic Dispensary

Email: 2903410@mail.ru

Department Head, Sakhalin Regional Oncologic Dispensary

俄罗斯联邦, Yuzhno-Sakhalinsk

Tatyana Sannikova

Perm Regional Hospital

Email: doctoron@mail.ru
ORCID iD: 0009-0002-6328-7785

oncologist

俄罗斯联邦, Perm

Alexandr Bystrov

Moscow City Oncology Hospital No. 62 of the Moscow City Health Department Istra

Email: mux19@yandex.ru

Cand. Sci. (Med.)

俄罗斯联邦, Krasnogorsk

Daria Dubovichenko

Arkhangelsk Clinical Oncologic Dispensary

Email: dubovichenko27@yandex.ru
ORCID iD: 0000-0002-1287-0279

Cand. Sci. (Med.)

俄罗斯联邦, Arkhangelsk

Mukhitova 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.)

俄罗斯联邦, Kazan

Viacheslav 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.)

俄罗斯联邦, Saint Petersburg

Konstantin Shkret

Central City Clinical Hospital No. 24

Email: kot_pvl@mail.ru
ORCID iD: 0009-0009-6547-9095

oncologist

俄罗斯联邦, Ekaterinburg

Mariya Gorshenina

Republican Oncologic Dispensary

Email: mivoLkova@rambler.ru

Department Head, Republican Oncologic Dispensary

俄罗斯联邦, Yoshkar-Ola

Mavzhuda 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

俄罗斯联邦, Kazan

Alina Kosareva

Multidisciplinary Clinical Medical Center „Medical City"

Email: 79136786767@yandex.ru
ORCID iD: 0009-0002-6863-247X

Oncologist

俄罗斯联邦, Tyumen

Olga Lutoshkina

Perm Regional Oncologic Dispensary

Email: Lutocomm@yandex.ru
ORCID iD: 0009-0009-9188-7199

clinical pharmacologist

俄罗斯联邦, Perm

Oxana Maslova

Odintsovo Regional Hospital

Email: mivoLkova@rambler.ru

oncologist, Department Head, Odintsovo Regional Hospital

俄罗斯联邦, Odintsovo

Maria Makhnutina

Samara Regional Clinical Oncologic Dispensary

Email: MahnutinaMV@mail.ru

oncologist, Samara Regional Clinical Oncologic Dispensary

俄罗斯联邦, Samara

Anna Mishina

Sverdlovsk Regional Oncologic Dispensary

Email: ya.a-nozdrina2016@yandex.ru
ORCID iD: 0009-0002-0311-1817

oncologist

俄罗斯联邦, Ekaterinburg

Makhabbat Murzalina

Orenburg Regional Clinical Oncologic Dispensary

Email: tyulegenova88@mail.ru
ORCID iD: 0000-0003-0078-7467

Department Head

俄罗斯联邦, Orenburg

Oksana Podyacheva

Regional Clinical Oncologic Dispensary

Email: doc_ox@mail.ru

Cand. Sci. (Med.), Regional Clinical Oncologic Dispensary

俄罗斯联邦, Ulyanovsk

Sergey 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.)

俄罗斯联邦, Moscow; Moscow

Ovsep 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

俄罗斯联邦, Moscow

Alfiya 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

俄罗斯联邦, Kazan

Ksenia Semenova

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

Email: semenowa.xenya2016@yandex.ru
ORCID iD: 0009-0002-0764-7790

oncologist

俄罗斯联邦, Chelyabinsk

Mariya Strokova

Efetov Crimean Republican Oncologic Clinical Dispensary

Email: strokovamaria@mail.ru
ORCID iD: 0000-0002-3360-3401

Department Head

俄罗斯联邦, Simferopol

Ekaterina Urashkina

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

Email: U_Kate_1992@mail.ru
ORCID iD: 0009-0003-5085-5138

oncologist

俄罗斯联邦, Chelyabinsk

Olesya Shmygina

Lotos Medical Center LLC

Email: iva8439@yandex.ru
ORCID iD: 0009-0007-4875-3203

oncologist

俄罗斯联邦, Chelyabinsk

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2. Fig. 1. Timing of onset and resolution of AEs during therapy with lenvatinib and pembrolizumab in 151 patients with advanced RCC.

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