Efficacy of the combination of lenvatinib with pembrolizumab in patients with advanced renal cell carcinoma
M. I. Volkova,
A. S. Kalpinskiy,
О. A. Goncharova,
К. V. Menshikov,
O. A. Stativko,
E. V. Karabina,
A. S. Dergunov,
N. I. Polshina,
E. N. Aleksandrova,
A. A. Lebedinets,
A. K. Panov,
A. V. Sultanbaev,
E. A. Usynin,
M. V. Volkonsky,
V. V. Mikhalyuk,
R. A. Zukov,
Yu. V. Anzhiganova,
M. A. Gusniev,
E. N. Igumnova,
S. V. Kuzmicheva,
I. A. Pokataev,
A. S. Olshanskaya,
N. I. Pervakova,
E. L. Parsadanova,
T. A. Sannikova,
A. A. Bystrov,
D. M. Dubovichenko,
M. R. Mukhitova,
V. A. Chubenko,
K. A. Shkret,
M. N. Gorshenina,
A. V. Semenov,
M. K. Davlatova,
A. E. Kosareva,
O. A. Lutoshkina,
O. A. Maslova,
M. V. Makhnutina,
A. V. Mishina,
M. Zh. Murzalina,
O. A. Podyacheva,
S. A. Kalinin,
O. A. Mailyan,
A. R. Safarova,
K. O. Semenova,
M. A. Strokova,
E. Yu. Urashkina,
O. S. Shmygina,
O. Yu. Novikova https://doi.org/10.17650/1726-9776-2024-20-3-33-48
Abstract
Objective: to re-evaluate the efficacy and safety of lenvatinib with pembrolizumab in unselected Russian renal cell carcinoma (RCC) patients, included in the phase IV study, in a median follow-up extended to 17.1 months. The primary end point was progression-free survival (PFS), secondary end points were overall survival (OS), objective response rate (ORR) and duration of response (DOR), disease control rate (DCR) and its duration, as well as safety.
Materials and methods. The study included medical data of 165 patients with verified advanced RCC who received lenvatinib with pembrolizumab in 36 centers of the Russian Federation from 05.02.2018 to 25.07.2024. The median age was 60 (20–76) years, the male to female ratio was 2.3:1. The majority of patients had Karnofsky performance status ³80 % (74.6 %), clear cell RCC (93.3 %) without sarcomatoid differentiation (93.3 %), metachronous metastases (50.9 %) localized in >1 organ (75.2 %), were nephrectomized (63.0 %) and did not receive antitumor therapy (91.0 %). At the time of lenvatinib with pembrolizumab therapy start 40 patients (24.2 %) were classified into International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable prognostic group, 92 (55.8 %) in the intermediate prognostic group, and 33 (20.0 %) in the poor prognostic group. The median follow-up was 17.1 (1.5–72.9) months.
Results. The median PFS achieved 24.0 (18.7–29.3) months, 17-month PFS 60.5 %. The median OS was 48.9 (18.5– 79.2) months, 17-month OS – 76.1 %. Objective response was registered in 46.0 % of patients including 2.4 % complete responders; the DCR was 92.1 %. The median DOR was 16.6 (2.1–72.9) months, duration of disease control –
14.3 (2.1–72.9) months. Confirmed dynamics of change in the sum of tumor foci diameters was recorded in 152 patients, while the median change was –25 % (from –100 % to +29 %). Any decrease in the sum of tumor foci diameters occurred in 69.1 % of cases. The incidence of any adverse events (AE) was 78.2 %, severe AE – 24.2 %, and serious AE – 9.7 %. Immune-mediated AEs developed in 17.0 % of cases and AE grades 3–4 in 6.7 % of cases. Mortality from AEs was 1.2 %.
Conclusion. Compared with the registration study, in real-world clinical practice in patients with advanced RCC the lenvatinib with pembrolizumab provides a lower ORR with comparable PFS and OS rates and demonstrates a satisfactory safety profile.
About the Authors
M. I. Volkova
City Clinical Oncological Hospital No. 1, Moscow Healthcare Department;
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation
Russian Federation
Mariya I. Volkova
18A Zagorodnoe Shosse, Moscow 117152,
Build. 1, 2/1 Barrikadnaya St., Moscow 125993
A. S. Kalpinskiy
P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation
Russian Federation
3 2nd Botkinskiy Proezd, Moscow 125284
О. A. Goncharova
Clinical Oncological Dispensary No. 1, Ministry of Health of Krasnodar region
Russian Federation
Russian Federation
146 Dimitrova St., Krasnodar 350040
К. V. Menshikov
Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Bashkortostan;
Bashkir State Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
73/1 Oktyabrya Prospekt, Ufa, Republic of Bashkortostan 450054,
3 Lenina St., Ufa, Republic of Bashkortostan 450008
O. A. Stativko
City Clinical Oncological Hospital No. 1, Moscow Healthcare Department
Russian Federation
Russian Federation
18A Zagorodnoe Shosse, Moscow 117152
E. V. Karabina
Tula Regional Clinical Oncological Dispensary
Russian Federation
Russian Federation
60 Kaluzhskoe shosse, Tula 300024
A. S. Dergunov
Tver Regional Clinical Oncological Dispensary
Russian Federation
Russian Federation
N. I. Polshina
A.S. Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department
Russian Federation
Russian Federation
86 Shosse Entuziastov, Moscow 111123
E. N. Aleksandrova
Yakutsk Republican Oncological Dispensary
Russian Federation
Russian Federation
89/5 Petra Alekseeva, Yakutsk 677005
A. A. Lebedinets
Leningrad Regional Clinical Hospital
Russian Federation
Russian Federation
Lit. A, Build. 1, 45 Prospekt Lunacharskogo, Saint Petersburg 194291
A. K. Panov
M.S. Rappoport Kuzbass Clinical Oncological Dispensary
Russian Federation
Russian Federation
25 Kutuzova St., Novokuznetsk 654041
A. V. Sultanbaev
Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Bashkortostan
Russian Federation
Russian Federation
73/1 Oktyabrya Prospekt, Ufa, Republic of Bashkortostan 450054
E. A. Usynin
Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Russian Federation
10 Naberezhnaya reki Ushaiki St., Tomsk 634050
M. V. Volkonsky
Moscow City Oncology Hospital No. 62, Moscow Healthcare Department
Russian Federation
Russian Federation
27 Istra, Moscow Region 143515
V. V. Mikhalyuk
Nizhnevartovsk Cancer Dispensary
Russian Federation
Russian Federation
9а Sportivnaya St., Nizhnevartovsk 628615
R. A. Zukov
V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia;
A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncological Dispensary
Russian Federation
Russian Federation
1 Partizana Zheleznyaka St., Krasnoyarsk 660022,
16 1st Smolenskaya St., Krasnoyarsk 660133
Yu. V. Anzhiganova
V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia;
A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncological Dispensary
Russian Federation
Russian Federation
1 Partizana Zheleznyaka St., Krasnoyarsk 660022,
16 1st Smolenskaya St., Krasnoyarsk 660133
M. A. Gusniev
Republican Oncology Center
Russian Federation
Russian Federation
24 Gaydara Gadzhieva St., Makhachkala, Republic of Dagestan 367008
E. N. Igumnova
Perm Regional Oncological Dispensary
Russian Federation
Russian Federation
15 Baumana St., Perm 614066
S. V. Kuzmicheva
Moscow Regional Oncological Dispensary
Russian Federation
Russian Federation
6 Karbysheva St., Balashikha 143900
I. A. Pokataev
City Clinical Oncological Hospital No. 1, Moscow Healthcare Department
Russian Federation
Russian Federation
18A Zagorodnoe Shosse, Moscow 117152
A. S. Olshanskaya
City Clinical Oncological Hospital No. 1, Moscow Healthcare Department
Russian Federation
Russian Federation
18A Zagorodnoe Shosse, Moscow 117152
N. I. Pervakova
M.S. Rappoport Kuzbass Clinical Oncological Dispensary
Russian Federation
Russian Federation
35 Volgogradskaya St., Kemerovo 650036
E. L. Parsadanova
Sakhalin Regional Oncological Dispensary
Russian Federation
Russian Federation
3 Gor’kogo St., Yuzhno-Sakhalinsk 693010
T. A. Sannikova
Perm Krai Clinical Hospital
Russian Federation
Russian Federation
85 Pushkina St., Perm 614990
A. A. Bystrov
Moscow City Oncology Hospital No. 62, Moscow Healthcare Department
Russian Federation
Russian Federation
27 Istra, Moscow Region 143515
D. M. Dubovichenko
Arkhangelsk Clinical Oncological Dispensary
Russian Federation
Russian Federation
Build. 1, 145 Proezd Obvodnyy Kanal, Arkhangelsk 163045
M. R. Mukhitova
Prof. M.Z. Sigal Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Tatarstan
Russian Federation
Russian Federation
29 Sibirskiy Trakt, Kazan, Republic of Tatarstan 420029
V. A. Chubenko
N.P. Napalkov Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)
Russian Federation
Russian Federation
lit. A, 68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758
K. A. Shkret
Central City Clinical Hospital No. 24
Russian Federation
Russian Federation
16 Rizhskiy Pereulok, Yekaterinburg 620085
M. N. Gorshenina
Republican Clinical Oncological Dispensary
Russian Federation
Russian Federation
22 Osipenko St., Yoshkar-Ola 424037
A. V. Semenov
Ivanovo Regional Oncological Dispensary
Russian Federation
Russian Federation
5 Lyubimova St., Ivanovo 153040
M. K. Davlatova
Prof. M.Z. Sigal Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Tatarstan
Russian Federation
Russian Federation
29 Sibirskiy Trakt, Kazan, Republic of Tatarstan 420029
A. E. Kosareva
Multidisciplinary Clinical Medical Center “Medical City”
Russian Federation
Russian Federation
32 Barnaul’skaya St., Tyumen 625041
O. A. Lutoshkina
Perm Regional Oncological Dispensary
Russian Federation
Russian Federation
15 Baumana St., Perm 614066
O. A. Maslova
Moscow Regional Oncological Dispensary
Russian Federation
Russian Federation
6 Karbysheva St., Balashikha 143900
M. V. Makhnutina
Samara Regional Clinical Oncological Dispensary
Russian Federation
Russian Federation
50 Solnechnaya St., Samara 443031
A. V. Mishina
Sverdlovsk Regional Oncological Dispensary
Russian Federation
Russian Federation
29 Soboleva St., Yekaterinburg 620036
M. Zh. Murzalina
Orenburg Regional Clinical Oncological Dispensary
Russian Federation
Russian Federation
11 Prospekt Gagarina, Orenburg 460021
O. A. Podyacheva
Regional Clinical Oncological Dispensary
Russian Federation
Russian Federation
90 12 Sentyabrya St., Ulyanovsk 432017
S. A. Kalinin
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation
Russian Federation
1 Ostrovityanova St., Moscow 117513
O. A. Mailyan
P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation
Russian Federation
3 2nd Botkinskiy Proezd, Moscow 125284
A. R. Safarova
Prof. M.Z. Sigal Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Tatarstan
Russian Federation
Russian Federation
29 Sibirskiy Trakt, Kazan, Republic of Tatarstan 420029
K. O. Semenova
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Russian Federation
Russian Federation
42 Blyukhera St., Chelyabinsk 454087
M. A. Strokova
V.M. Efetov Crimean Republican Oncological Clinical Dispensary
Russian Federation
Russian Federation
49A Bespalova St., Simferopol, Republic of Crimea 295023
E. Yu. Urashkina
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Russian Federation
Russian Federation
42 Blyukhera St., Chelyabinsk 454087
O. S. Shmygina
Medical Center “Lotus”
Russian Federation
Russian Federation
4 Engel’sa St., Chelyabinsk 454080
O. Yu. Novikova
Regional Clinical Center of Oncology
Russian Federation
Russian Federation
164 Voronezhskoe Shosse, Khabarovsk 680042
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For citations:
Volkova M.I., Kalpinskiy A.S., Goncharova О.A., Menshikov К.V., Stativko O.A., Karabina E.V., Dergunov A.S., Polshina N.I., Aleksandrova E.N., Lebedinets A.A., Panov A.K., Sultanbaev A.V., Usynin E.A., Volkonsky M.V., Mikhalyuk V.V., Zukov R.A., Anzhiganova Yu.V., Gusniev M.A., Igumnova E.N., Kuzmicheva S.V., Pokataev I.A., Olshanskaya A.S., Pervakova N.I., Parsadanova E.L., Sannikova T.A., Bystrov A.A., Dubovichenko D.M., Mukhitova M.R., Chubenko V.A., Shkret K.A., Gorshenina M.N., Semenov A.V., Davlatova M.K., Kosareva A.E., Lutoshkina O.A., Maslova O.A., Makhnutina M.V., Mishina A.V., Murzalina M.Zh., Podyacheva O.A., Kalinin S.A., Mailyan O.A., Safarova A.R., Semenova K.O., Strokova M.A., Urashkina E.Yu., Shmygina O.S., Novikova O.Yu. Efficacy of the combination of lenvatinib with pembrolizumab in patients with advanced renal cell carcinoma. Cancer Urology. 2024;20(3):33-48. (In Russ.) https://doi.org/10.17650/1726-9776-2024-20-3-33-48
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