Efficacy and safety of lenvatinib and everolimus combination in patients with metastatic renal cell carcinoma progression following targeted antiangiogenic therapy: secondary analysis of data obtained in the Russian multicenter observational study

M. I. Volkova; Волкова М. И.; A. S. Kalpinskiy; Калпинский А. С.; P. S. Borisov; Борисов П. С.; O. I. Evsyukova; Евсюкова О. И.; A. S. Olshanskaya; Ольшанская А. С.; V. B. Matveev; Матвеев В. Б.; B. Ya. Alekseev; Алексеев Б. Я.; E. V. Peganova; Пеганова Е. В.; A. F. Nasretdinov; Насретдинов А. Ф.; E. V. Lymar; Лымарь Е. В.; E. G. Ovchinnikova; Овчинникова Е. Г.; T. A. Sveklina; Свеклина Т. А.; E. A. Usynin; Усынин Е. А.; A. M. Abdelgafur; Абдельгафур A. М.; E. A. Tararova; Тарарова Е. А.; L. M. Shumova; Шумова Л. М.; A. S. Belenkov; Беленков А. С.; I. Yu. Dolgov; Долгов И. Ю.; N. G. Ponomareva; Пономарева Н. Г.; I. V. Evstigneeva; Евстигнеева И. В.; A. N. Ivanov; Иванов А. Н.; A. R. Isaev; Исаев А. Р.; R. V. Leonenkov; Леоненков Р. В.; A. V. Meskikh; Меских А. В.; M. R. Mukhitova; Мухитова М. Р.; S. A. Orlova; Орлова С. А.; I. V. Teslenok; Тесленок И. В.; M. M. Shegurova; Шегурова М. М.; M. T. Aivazov; Айвазов М. Т.; Z. V. Amoev; Амоев З. В.; K. G. Babina; Бабина К. Г.; A. A. Vorontsova; Воронцова А. А.; E. V. Karabina; Карабина Е. В.; N. V. Kirdakova; Кирдакова Н. В.; I. E. Shumskaya; Шумская И. Э.; G. P. Kolesnikov; Колесников Г. П.; E. S. Kuzmina; Кузьмина Е. С.; D. Kh. Latipova; Латипова Д. Х.; E. S. Lyutova; Лютова Е. С.; M. M. Fael; Фаэль М. М.; A. N Chugarova; Чугарова А. Н.; A. S. Antipin; Антипин А. С.

doi:10.17650/1726-9776-2021-17-1-31-44

Efficacy and safety of lenvatinib and everolimus combination in patients with metastatic renal cell carcinoma progression following targeted antiangiogenic therapy: secondary analysis of data obtained in the Russian multicenter observational study

Authors: Volkova M.I.¹, Kalpinskiy A.S.², Borisov P.S.³, Evsyukova O.I.¹, Olshanskaya A.S.¹, Matveev V.B.¹, Alekseev B.Y.²^,4, Peganova E.V.⁵, Nasretdinov A.F.⁶, Lymar E.V.⁷, Ovchinnikova E.G.⁸, Sveklina T.A.⁸, Usynin E.A.⁹, Abdelgafur A.M.¹⁰, Tararova E.A.⁸, Shumova L.M.⁸, Belenkov A.S.⁸, Dolgov I.Y.¹⁰, Ponomareva N.G.⁸, Evstigneeva I.V.¹¹, Ivanov A.N.¹⁰, Isaev A.R.¹², Leonenkov R.V.¹³, Meskikh A.V.¹³, Mukhitova M.R.¹⁴, Orlova S.A.¹⁰, Teslenok I.V.¹², Shegurova M.M.⁸, Aivazov M.T.¹⁵, Amoev Z.V.¹⁶, Babina K.G.¹⁷, Vorontsova A.A.¹⁵, Karabina E.V.¹⁸, Kirdakova N.V.¹⁹, Shumskaya I.E.¹⁹, Kolesnikov G.P.²⁰, Kuzmina E.S.²¹, Latipova D.K.², Lyutova E.S.⁸, Fael M.M.²², Chugarova A.N¹¹, Antipin A.S.²³
Affiliations:
1. N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
2. P.A. Hertzen Moscow Oncology Research Institute — branch of the National Medical Research Radiological Center, Ministry of Health of Russia
3. N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
4. Medical Institute of Continuing Education, Moscow State University of Food Production
5. Regional Clinical Oncology Hospital
6. Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Bashkortostan
7. Clinical Oncology Dispensary No. 1, Ministry of Health of Krasnodar Region
8. Nizhny Novgorod Regional Clinical Oncology Dispensary
9. Tomsk National Research Medical Center of the Russian Academy of Sciences
10. Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia
11. Tver Regional Clinical Oncology Dispensary
12. Outpatient Cancer Care Center, D.D. Pletnev City Clinical Hospital, Moscow Healthcare Department
13. Sain-Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
14. Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Tatarstan
15. Oncology Center No. 4, Moscow Healthcare Department
16. Volga Regional Medical Center, Federal Biomedical Agency of Russia
17. Volgograd Regional Clinical Oncology Center
18. Tula Regional Oncology Dispensary
19. City Clinical Oncology Hospital No. 1, Moscow Healthcare Department
20. Moscow City Oncology Hospital No. 62, Moscow Healthcare Department
21. Salekhard Regional Clinical Hospital
22. City Polyclinic No. 11, Moscow Healthcare Department
23. Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Issue: Vol 17, No 1 (2021)
Pages: 31-44
Section: DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER
Published: 02.05.2021
URL: https://oncourology.abvpress.ru/oncur/article/view/1440
DOI: https://doi.org/10.17650/1726-9776-2021-17-1-31-44
ID: 1440

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Abstract
About the authors
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Abstract

Objective. The primary endpoint was progression-free survival; secondary endpoints included overall survival, objective response rate and duration, tumor control rate and duration, as well as safety profile of lenvatinib with everolimus in consecutive patients with advanced renal cell carcinoma who had disease progression after targeted antiangiogenic therapy.

Materials and methods. This observational study included 129 consecutive patients with metastatic renal cell carcinoma resistant to targeted antiangiogenic therapy. The median age was 60 years; a male to female ratio was 3.1:1. Twenty-seven patients (20.9 %) had ECOG performance status of 2—4. The majority of study participants (n = 127; 98.4 %) had multiple metastases. Tumor lesions were located in >1 organ in 104 cases (80.6 %). The primary tumor was removed in 110 (85.3 %), including 39 (30.2 %) patients undergone cytoreductive surgery. Seventy patients (54.2 %) had earlier received more than one line of therapy. Upon enrollment, there were 13 IMDC favourable-risk patients (10.1 %), 86 IMDC intermediate-risk patients (66.6 %), and 29 IMDC poor-risk patients (22.5 %). In one patient (0.8 %), the IMDC risk was not estimated. All patients received lenvatinib at a dose of 18 mg/day and everolimus at a dose of 5 mg/day. The median follow-up was 10.5 (1—30) months.

Results. Median progression-free survival was 14.9 (11.9—17.9) months; overall survival was 19.9 (15.2—24.6) months. The objective response rate was 17.0 % (median duration 9.7 (2.8—16.5) months); tumor control rate was 72.9 % (median duration 10.0 (2.5—17.5) months). Adverse events were observed in 112patients (86.8 %) with grade III—IVadverse events registered in 27participants (20.9 %). Five participants (3.9 %) needed inpatient treatment of adverse events; one patient (0.8 %) died due to adverse events. Adverse events required treatment discontinuation in 4 patients (3.1 %), treatment interruption in 35 patients (27.1 %), and dose reduction in 33 patients (25.6 %).

Conclusion. The results of the secondary analysis in the ROSLERCM observational study confirmed the results obtained earlier on the efficacy and safety of the lenvatinib plus everolimus combination in the second- and subsequent-line therapy for advanced renal cell carcinoma resistant to targeted antiangiogenic therapy in consecutive Russian patients.

Keywords

drug-resistant disseminated renal cell carcinoma, second-line therapy, lenvatinib plus everolimus combination

About the authors

M. I. Volkova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

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

24 Kashirskoe Shosse, Moscow 115478.

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

P. S. Borisov

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0003-4267-2799

68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.

Russian Federation

O. I. Evsyukova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0002-3016-6357

24 Kashirskoe Shosse, Moscow 115478.

Russian Federation

A. S. Olshanskaya

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0003-0389-564X

24 Kashirskoe Shosse, Moscow 115478.

Russian Federation

V. B. Matveev

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0001-7748-9527

24 Kashirskoe Shosse, Moscow 115478.

Russian Federation

B. Ya. Alekseev

P.A. Hertzen Moscow Oncology Research Institute — branch of the National Medical Research Radiological Center, Ministry of Health of Russia; Medical Institute of Continuing Education, Moscow State University of Food Production

ORCID iD: 0000-0002-3398-4128

3 2nd Botkinskiy Proezd, Moscow 125284; 11 Volokolamskoe Shosse, Moscow 125080.

Russian Federation

E. V. Peganova

Regional Clinical Oncology Hospital

67 Prospekt Oktyabrya, Yaroslavl 150054.

Russian Federation

A. F. Nasretdinov

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

ORCID iD: 0000-0001-8340-7962

73/1 Prospekt Oktyabrya, Ufa 450054.

Russian Federation

E. V. Lymar

Clinical Oncology Dispensary No. 1, Ministry of Health of Krasnodar Region

146 Dimitrova St., Krasnodar 350040.

Russian Federation

E. G. Ovchinnikova

Nizhny Novgorod Regional Clinical Oncology Dispensary

ORCID iD: 0000-0002-9254-8916

11/1 Delovaya St., Nizhny Novgorod 603093.

Russian Federation

T. A. Sveklina

Nizhny Novgorod Regional Clinical Oncology Dispensary

11/1 Delovaya St., Nizhny Novgorod 603093.

Russian Federation

E. A. Usynin

Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID iD: 0000-0001-7127-0188

5 Kooperativny Pereulok, Tomsk 634009.

Russian Federation

A. M. Abdelgafur

Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia

ORCID iD: 0000-0002-8917-5610

31 Gladkova St., Cheboksary 428020, Republic of Chuvashia.

Russian Federation

E. A. Tararova

Nizhny Novgorod Regional Clinical Oncology Dispensary

11/1 Delovaya St., Nizhny Novgorod 603093.

Russian Federation

L. M. Shumova

Nizhny Novgorod Regional Clinical Oncology Dispensary

11/1 Delovaya St., Nizhny Novgorod 603093.

Russian Federation

A. S. Belenkov

Nizhny Novgorod Regional Clinical Oncology Dispensary

11/1 Delovaya St., Nizhny Novgorod 603093.

Russian Federation

I. Yu. Dolgov

Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia

31 Gladkova St., Cheboksary 428020, Republic of Chuvashia.

Russian Federation

N. G. Ponomareva

Nizhny Novgorod Regional Clinical Oncology Dispensary

11/1 Delovaya St., Nizhny Novgorod 603093.

Russian Federation

I. V. Evstigneeva

Tver Regional Clinical Oncology Dispensary

57/37 15 let Oktyabrya St., Tver 170008.

Russian Federation

A. N. Ivanov

Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia

31 Gladkova St., Cheboksary 428020, Republic of Chuvashia.

Russian Federation

A. R. Isaev

Outpatient Cancer Care Center, D.D. Pletnev City Clinical Hospital, Moscow Healthcare Department

32 11th Parkovaya St., Moscow 105077.

Russian Federation

R. V. Leonenkov

Sain-Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)

ORCID iD: 0000-0001-9710-2406

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

Russian Federation

A. V. Meskikh

Sain-Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)

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

Russian Federation

M. R. Mukhitova

Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Tatarstan

ORCID iD: 0000-0002-0741-624X

29 Sibirskiy Trakt St., Kazan 420029.

Russian Federation

S. A. Orlova

Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia

31 Gladkova St., Cheboksary 428020, Republic of Chuvashia.

Russian Federation

I. V. Teslenok

Outpatient Cancer Care Center, D.D. Pletnev City Clinical Hospital, Moscow Healthcare Department

32 11th Parkovaya St., Moscow 105077.

Russian Federation

M. M. Shegurova

Nizhny Novgorod Regional Clinical Oncology Dispensary

11/1 Delovaya St., Nizhny Novgorod 603093.

Russian Federation

M. T. Aivazov

Oncology Center No. 4, Moscow Healthcare Department

ORCID iD: 0000-0003-3293-1697

7 Medikov St., Moscow 115304.

Russian Federation

Z. V. Amoev

Volga Regional Medical Center, Federal Biomedical Agency of Russia

ORCID iD: 0000-0003-3510-4611

2 Nizhnevolzhskaya Naberezhnaya, Nizhny Novgorod 603001.

Russian Federation

K. G. Babina

Volgograd Regional Clinical Oncology Center

78 im. Zemlyachki St., Volgograd 400138.

Russian Federation

A. A. Vorontsova

Oncology Center No. 4, Moscow Healthcare Department

7 Medikov St., Moscow 115304.

Russian Federation

E. V. Karabina

Tula Regional Oncology Dispensary

ORCID iD: 0000-0001-6062-5318

201A Plekhanova St., Tula 300040.

Russian Federation

N. V. Kirdakova

City Clinical Oncology Hospital No. 1, Moscow Healthcare Department

ORCID iD: 0000-0001-8233-9224

17/1 Baumanskaya St., Moscow 105005.

Russian Federation

I. E. Shumskaya

City Clinical Oncology Hospital No. 1, Moscow Healthcare Department

17/1 Baumanskaya St., Moscow 105005.

Russian Federation

G. P. Kolesnikov

Moscow City Oncology Hospital No. 62, Moscow Healthcare Department

ORCID iD: 0000-0002-1272-9136

27 Istra, Moscow region 143423.

Russian Federation

E. S. Kuzmina

Salekhard Regional Clinical Hospital

ORCID iD: 0000-0001-8979-2208

39 Mira St., Salekhard 629001.

Russian Federation

D. Kh. Latipova

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

ORCID iD: 0000-0002-8906-0370

3 2nd Botkinskiy Proezd, Moscow 125284.

Russian Federation

E. S. Lyutova

Nizhny Novgorod Regional Clinical Oncology Dispensary

11/1 Delovaya St., Nizhny Novgorod 603093.

Russian Federation

M. M. Fael

City Polyclinic No. 11, Moscow Healthcare Department

ORCID iD: 0000-0001-7588-665X

14 Kravchenko St., Moscow 119331.

Russian Federation

A. N Chugarova

Tver Regional Clinical Oncology Dispensary

57/37 15 let Oktyabrya St., Tver 170008.

Russian Federation

A. S. Antipin

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

ORCID iD: 0000-0003-3147-7023

42 Blyukhera St., Chelyabinsk 454087.

Russian Federation

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