Efficacy of the combination of lenvatinib with pembrolizumab in patients with advanced renal cell carcinoma

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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

Author for correspondence.
Email: mivolkova@rambler.ru
ORCID iD: 0000-0001-7754-6624

Mariya I. Volkova 

18A Zagorodnoe Shosse, Moscow 117152, 

Build. 1, 2/1 Barrikadnaya St., Moscow 125993

Russian Federation

A. S. Kalpinskiy

P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia

ORCID iD: 0000-0002-2209-3020

3 2nd Botkinskiy Proezd, Moscow 125284

Russian Federation

О. A. Goncharova

Clinical Oncological Dispensary No. 1, Ministry of Health of Krasnodar region

ORCID iD: 0000-0002-6322-7144

146 Dimitrova St., Krasnodar 350040

Russian Federation

К. V. Menshikov

Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Bashkortostan;
Bashkir State Medical University, Ministry of Health of Russia

ORCID iD: 0000-0003-3734-2779

73/1 Oktyabrya Prospekt, Ufa, Republic of Bashkortostan 450054, 

3 Lenina St., Ufa, Republic of Bashkortostan 450008

Russian Federation

O. A. Stativko

City Clinical Oncological Hospital No. 1, Moscow Healthcare Department

ORCID iD: 0009-0002-1084-1551

18A Zagorodnoe Shosse, Moscow 117152

Russian Federation

E. V. Karabina

Tula Regional Clinical Oncological Dispensary

ORCID iD: 0000-0001-6062-5318

60 Kaluzhskoe shosse, Tula 300024

Russian Federation

A. S. Dergunov

Tver Regional Clinical Oncological Dispensary

170008 Тверь, ул. 15 лет Октября, 57/37

Russian Federation

N. I. Polshina

A.S. Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

ORCID iD: 0000-0001-5417-0425

86 Shosse Entuziastov, Moscow 111123

Russian Federation

E. N. Aleksandrova

Yakutsk Republican Oncological Dispensary

89/5 Petra Alekseeva, Yakutsk 677005

Russian Federation

A. A. Lebedinets

Leningrad Regional Clinical Hospital

ORCID iD: 0009-0002-0240-6656

Lit. A, Build. 1, 45 Prospekt Lunacharskogo, Saint Petersburg 194291

Russian Federation

A. K. Panov

M.S. Rappoport Kuzbass Clinical Oncological Dispensary

25 Kutuzova St., Novokuznetsk 654041

Russian Federation

A. V. Sultanbaev

Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Bashkortostan

ORCID iD: 0000-0003-0996-5995

73/1 Oktyabrya Prospekt, Ufa, Republic of Bashkortostan 450054

Russian Federation

E. A. Usynin

Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID iD: 0000-0001-7127-0188

10 Naberezhnaya reki Ushaiki St., Tomsk 634050

Russian Federation

M. V. Volkonsky

Moscow City Oncology Hospital No. 62, Moscow Healthcare Department

ORCID iD: 0000-0003-4060-5015

27 Istra, Moscow Region 143515

Russian Federation

V. V. Mikhalyuk

Nizhnevartovsk Cancer Dispensary

ORCID iD: 0009-0006-0220-085X

9а Sportivnaya St., Nizhnevartovsk 628615

Russian Federation

R. A. Zukov

V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia;
A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncological Dispensary

ORCID iD: 0000-0003-1576-5930

1 Partizana Zheleznyaka St., Krasnoyarsk 660022,

16 1st Smolenskaya St., Krasnoyarsk 660133

Russian Federation

Yu. V. Anzhiganova

V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Ministry of Health of Russia;
A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncological Dispensary

ORCID iD: 0000-0002-8388-466X

1 Partizana Zheleznyaka St., Krasnoyarsk 660022,

16 1st Smolenskaya St., Krasnoyarsk 660133

Russian Federation

M. A. Gusniev

Republican Oncology Center

ORCID iD: 0000-0001-9538-8869

24 Gaydara Gadzhieva St., Makhachkala, Republic of Dagestan 367008

Russian Federation

E. N. Igumnova

Perm Regional Oncological Dispensary

ORCID iD: 0009-0007-3428-9585

15 Baumana St., Perm 614066

Russian Federation

S. V. Kuzmicheva

Moscow Regional Oncological Dispensary

6 Karbysheva St., Balashikha 143900

Russian Federation

I. A. Pokataev

City Clinical Oncological Hospital No. 1, Moscow Healthcare Department

ORCID iD: 0000-0001-9864-3837

18A Zagorodnoe Shosse, Moscow 117152

Russian Federation

A. S. Olshanskaya

City Clinical Oncological Hospital No. 1, Moscow Healthcare Department

ORCID iD: 0000-0003-0389-564X

18A Zagorodnoe Shosse, Moscow 117152

Russian Federation

N. I. Pervakova

M.S. Rappoport Kuzbass Clinical Oncological Dispensary

35 Volgogradskaya St., Kemerovo 650036

Russian Federation

E. L. Parsadanova

Sakhalin Regional Oncological Dispensary

3 Gor’kogo St., Yuzhno-Sakhalinsk 693010

Russian Federation

T. A. Sannikova

Perm Krai Clinical Hospital

ORCID iD: 0009-0002-6328-7785

85 Pushkina St., Perm 614990

Russian Federation

A. A. Bystrov

Moscow City Oncology Hospital No. 62, Moscow Healthcare Department

27 Istra, Moscow Region 143515

Russian Federation

D. M. Dubovichenko

Arkhangelsk Clinical Oncological Dispensary

ORCID iD: 0000-0002-1287-0279

Build. 1, 145 Proezd Obvodnyy Kanal, Arkhangelsk 163045

Russian Federation

M. R. Mukhitova

Prof. M.Z. Sigal Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Tatarstan

ORCID iD: 0000-0002-0741-624X

29 Sibirskiy Trakt, Kazan, Republic of Tatarstan 420029

Russian Federation

V. A. Chubenko

N.P. Napalkov Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)

ORCID iD: 0000-0001-6644-6687

lit. A, 68A Leningradskaya St., Pesochnyy, Saint Petersburg 197758

Russian Federation

K. A. Shkret

Central City Clinical Hospital No. 24

ORCID iD: 0009-0009-6547-9095

16 Rizhskiy Pereulok, Yekaterinburg 620085

Russian Federation

M. N. Gorshenina

Republican Clinical Oncological Dispensary

22 Osipenko St., Yoshkar-Ola 424037

Russian Federation

A. V. Semenov

Ivanovo Regional Oncological Dispensary

ORCID iD: 0000-0002-5510-3336

5 Lyubimova St., Ivanovo 153040

Russian Federation

M. K. Davlatova

Prof. M.Z. Sigal Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Tatarstan

ORCID iD: 0009-0008-3082-8569

29 Sibirskiy Trakt, Kazan, Republic of Tatarstan 420029

Russian Federation

A. E. Kosareva

Multidisciplinary Clinical Medical Center “Medical City”

ORCID iD: 0009-0002-6863-247X

32 Barnaul’skaya St., Tyumen 625041

Russian Federation

O. A. Lutoshkina

Perm Regional Oncological Dispensary

ORCID iD: 0009-0009-9188-7199

15 Baumana St., Perm 614066

Russian Federation

O. A. Maslova

Moscow Regional Oncological Dispensary

6 Karbysheva St., Balashikha 143900

Russian Federation

M. V. Makhnutina

Samara Regional Clinical Oncological Dispensary

50 Solnechnaya St., Samara 443031

Russian Federation

A. V. Mishina

Sverdlovsk Regional Oncological Dispensary

ORCID iD: 0009-0002-0311-1817

29 Soboleva St., Yekaterinburg 620036

Russian Federation

M. Zh. Murzalina

Orenburg Regional Clinical Oncological Dispensary

ORCID iD: 0000-0003-0078-7467

11 Prospekt Gagarina, Orenburg 460021

Russian Federation

O. A. Podyacheva

Regional Clinical Oncological Dispensary

90 12 Sentyabrya St., Ulyanovsk 432017

Russian Federation

S. A. Kalinin

N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia

ORCID iD: 0000-0002-0694-7911

1 Ostrovityanova St., Moscow 117513

Russian Federation

O. A. Mailyan

P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia

ORCID iD: 0000-0002-9787-8842

3 2nd Botkinskiy Proezd, Moscow 125284

Russian Federation

A. R. Safarova

Prof. M.Z. Sigal Republican Clinical Oncological Dispensary, Ministry of Health of the Republic of Tatarstan

ORCID iD: 0000-0002-2988-3746

29 Sibirskiy Trakt, Kazan, Republic of Tatarstan 420029

Russian Federation

K. O. Semenova

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

ORCID iD: 0009-0002-0764-7790

42 Blyukhera St., Chelyabinsk 454087

Russian Federation

M. A. Strokova

V.M. Efetov Crimean Republican Oncological Clinical Dispensary

ORCID iD: 0000-0002-3360-3401

49A Bespalova St., Simferopol, Republic of Crimea 295023

Russian Federation

E. Yu. Urashkina

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

ORCID iD: 0009-0003-5085-5138

42 Blyukhera St., Chelyabinsk 454087

Russian Federation

O. S. Shmygina

Medical Center “Lotus”

ORCID iD: 0009-0007-4875-3203

4 Engel’sa St., Chelyabinsk 454080

Russian Federation

O. Yu. Novikova

Regional Clinical Center of Oncology

ORCID iD: 0000-0002-0950-0648

164 Voronezhskoe Shosse, Khabarovsk 680042

Russian Federation

References

  1. Volkova M.I., Nosov D.A., Alekseev B.Ya. et al. Practical guidelines on drug treatment of renal cell carcinoma. Zlokachestvennye opukholi. Prakticheskie rekomendatsii RUSSCO = Malignant Tumors: RUSSCO Practical Guidelines 2023;13(3s2):609–19. (In Russ.).
  2. Motzer R.J., Jonasch E., Agarwal N. et al. nccn clinical practice guidelines in oncology. Kidney Cancer – v.1.2025. July 1, 2024.
  3. Motzer R., Alekseev B., Rha S.Y. 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
  4. Motzer R.J., 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
  5. 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
  6. 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. Lancet Oncol 2023;24(8):881–91. doi: 10.1016/S1470-2045(23)00276-0
  7. Volkova M.I., Kalpinskiy A.S., Goncharova O.A. et al. Toxicity and safety of the combination of lenvatinib with pembrolizumab in patients with advance renal cell cancer. Sovremennaya onkologiya = Journal of Modern Oncology 2024;26(1):39–47. (In Russ.).
  8. Lenvatinib instructions for use. Registration number: ЛП-003398- 060720. (In Russ.).
  9. Pembrolizumab instructions for use. Registration number: ЛП-008684, 2022. (In Russ.).
  10. Eisenhauer E.A., 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
  11. 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. Actas Dermosifiliogr (Engl Ed) 2021;112(1):90–2. doi: 10.1016/j.ad.2019.05.00
  12. Lee C.H., Yogesh Shah A., Rao A. et al. Final database lock results of the phase 2 cohort of lenvatinib + pembrolizumab for progressive disease after a PD-1/PD-L1-containing therapy in metastatic clear cell renal cell carcinoma. Oncologist 2023;28(Suppl 1):S3–4.
  13. Hamamoto S., Tasaki Y., Morikawa T. et al. Efficacy and safety of immuno-oncology plus tyrosine kinase inhibitors as late-line combination therapy for patients with advanced renal cell carcinoma. J Clin Med 2024;13(12):3365. doi: 10.3390/jcm13123365
  14. Liu Y., Zhou L., Chen Y. et al. Hypertension as a prognostic factor in metastatic renal cell carcinoma treated with tyrosine kinase inhibitors: a systematic review and meta-analysis. BMC Urol 2019;19(1):49. doi: 10.1186/s12894-019-0481-5
  15. Volkova M.I., Kalpinskiy A.S., Men’shikov K.V. et al. Efficacy and safety of cabozantinib in metastatic renal cell carcinoma patients: Russian multicenter observational study. Onkourologiya = Cancer Urology 2023;19(1):46–60. (In Russ.). doi: 10.17650/1726-9776-2023-19-1-46-60
  16. Ikeda T., Ishihara H., Nemoto Y. et al. Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Urol Oncol 2021;39(10):735.e9–5. doi: 10.1016/j.urolonc.2021.05.012
  17. Haight P.J., Brown M.D., Espelien B.M. et al. Predictors of toxicity and response to treatment with lenvatinib and pembrolizumab in patients with gynecologic malignancy. Presented at: Society of Gynecologic Oncology Winter Meeting; January 25–27, 2024; Olympic Valley, CA. Poster 509234.

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