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,
A. S. Kalpinskiy,
P. S. Borisov,
O. I. Evsyukova,
A. S. Olshanskaya,
V. B. Matveev,
B. Ya. Alekseev,
E. V. Peganova,
A. F. Nasretdinov,
E. V. Lymar,
E. G. Ovchinnikova,
T. A. Sveklina,
E. A. Usynin,
A. M. Abdelgafur,
E. A. Tararova,
L. M. Shumova,
A. S. Belenkov,
I. Yu. Dolgov,
N. G. Ponomareva,
I. V. Evstigneeva,
A. N. Ivanov,
A. R. Isaev,
R. V. Leonenkov,
A. V. Meskikh,
M. R. Mukhitova,
S. A. Orlova,
I. V. Teslenok,
M. M. Shegurova,
M. T. Aivazov,
Z. V. Amoev,
K. G. Babina,
A. A. Vorontsova,
E. V. Karabina,
N. V. Kirdakova,
I. E. Shumskaya,
G. P. Kolesnikov,
E. S. Kuzmina,
D. Kh. Latipova,
E. S. Lyutova,
M. M. Fael,
A. N Chugarova,
A. S. Antipin https://doi.org/10.17650/1726-9776-2021-17-1-31-44
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
Supporting agencies: The article was published with the financial support of Eisai Co., Ltd. The authors bear full responsibility for the content of the article and editorial decisions.
About the Authors
M. I. Volkova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
24 Kashirskoe Shosse, Moscow 115478.
Competing Interests:
No
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
Competing Interests:
Russian Federation
3 2nd Botkinskiy Proezd, Moscow 125284.
Competing Interests:
No
P. S. Borisov
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
68 Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.
Competing Interests:
No
O. I. Evsyukova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
24 Kashirskoe Shosse, Moscow 115478.
Competing Interests:
No
A. S. Olshanskaya
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
24 Kashirskoe Shosse, Moscow 115478.
Competing Interests:
No
V. B. Matveev
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
24 Kashirskoe Shosse, Moscow 115478.
Competing Interests:
No
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
Russian Federation
Competing Interests:
Russian Federation
3 2nd Botkinskiy Proezd, Moscow 125284; 11 Volokolamskoe Shosse, Moscow 125080.
Competing Interests:
No
E. V. Peganova
Regional Clinical Oncology Hospital
Russian Federation
Competing Interests:
Russian Federation
67 Prospekt Oktyabrya, Yaroslavl 150054.
Competing Interests:
No
A. F. Nasretdinov
Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Bashkortostan
Russian Federation
Competing Interests:
Russian Federation
73/1 Prospekt Oktyabrya, Ufa 450054.
Competing Interests:
No
E. V. Lymar
Clinical Oncology Dispensary No. 1, Ministry of Health of Krasnodar Region
Russian Federation
Competing Interests:
Russian Federation
146 Dimitrova St., Krasnodar 350040.
Competing Interests:
No
E. G. Ovchinnikova
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
11/1 Delovaya St., Nizhny Novgorod 603093.
Competing Interests:
No
T. A. Sveklina
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
11/1 Delovaya St., Nizhny Novgorod 603093.
Competing Interests:
No
E. A. Usynin
Tomsk National Research Medical Center of the Russian Academy of Sciences
Russian Federation
Competing Interests:
Russian Federation
5 Kooperativny Pereulok, Tomsk 634009.
Competing Interests:
No
A. M. Abdelgafur
Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia
Russian Federation
Competing Interests:
Russian Federation
31 Gladkova St., Cheboksary 428020, Republic of Chuvashia.
Competing Interests:
No
E. A. Tararova
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
11/1 Delovaya St., Nizhny Novgorod 603093.
Competing Interests:
No
L. M. Shumova
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
11/1 Delovaya St., Nizhny Novgorod 603093.
Competing Interests:
No
A. S. Belenkov
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
11/1 Delovaya St., Nizhny Novgorod 603093.
Competing Interests:
No
I. Yu. Dolgov
Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia
Russian Federation
Competing Interests:
Russian Federation
31 Gladkova St., Cheboksary 428020, Republic of Chuvashia.
Competing Interests:
No
N. G. Ponomareva
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
11/1 Delovaya St., Nizhny Novgorod 603093.
Competing Interests:
No
I. V. Evstigneeva
Tver Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
57/37 15 let Oktyabrya St., Tver 170008.
Competing Interests:
No
A. N. Ivanov
Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia
Russian Federation
Competing Interests:
Russian Federation
31 Gladkova St., Cheboksary 428020, Republic of Chuvashia.
Competing Interests:
No
A. R. Isaev
Outpatient Cancer Care Center, D.D. Pletnev City Clinical Hospital, Moscow Healthcare Department
Russian Federation
Competing Interests:
Russian Federation
32 11th Parkovaya St., Moscow 105077.
Competing Interests:
No
R. V. Leonenkov
Sain-Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
Russian Federation
Competing Interests:
Russian Federation
68A Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.
Competing Interests:
No
A. V. Meskikh
Sain-Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
Russian Federation
Competing Interests:
Russian Federation
68A Leningradskaya St., Pesochnyy, Saint-Petersburg 197758.
Competing Interests:
No
M. R. Mukhitova
Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Tatarstan
Russian Federation
Competing Interests:
Russian Federation
29 Sibirskiy Trakt St., Kazan 420029.
Competing Interests:
No
S. A. Orlova
Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia
Russian Federation
Competing Interests:
Russian Federation
31 Gladkova St., Cheboksary 428020, Republic of Chuvashia.
Competing Interests:
No
I. V. Teslenok
Outpatient Cancer Care Center, D.D. Pletnev City Clinical Hospital, Moscow Healthcare Department
Russian Federation
Competing Interests:
Russian Federation
32 11th Parkovaya St., Moscow 105077.
Competing Interests:
No
M. M. Shegurova
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
11/1 Delovaya St., Nizhny Novgorod 603093.
Competing Interests:
No
M. T. Aivazov
Oncology Center No. 4, Moscow Healthcare Department
Russian Federation
Competing Interests:
Russian Federation
7 Medikov St., Moscow 115304.
Competing Interests:
No
Z. V. Amoev
Volga Regional Medical Center, Federal Biomedical Agency of Russia
Russian Federation
Competing Interests:
Russian Federation
2 Nizhnevolzhskaya Naberezhnaya, Nizhny Novgorod 603001.
Competing Interests:
No
K. G. Babina
Volgograd Regional Clinical Oncology Center
Russian Federation
Competing Interests:
Russian Federation
78 im. Zemlyachki St., Volgograd 400138.
Competing Interests:
No
A. A. Vorontsova
Oncology Center No. 4, Moscow Healthcare Department
Russian Federation
Competing Interests:
Russian Federation
7 Medikov St., Moscow 115304.
Competing Interests:
No
E. V. Karabina
Tula Regional Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
201A Plekhanova St., Tula 300040.
Competing Interests:
No
N. V. Kirdakova
City Clinical Oncology Hospital No. 1, Moscow Healthcare Department
Russian Federation
Competing Interests:
Russian Federation
17/1 Baumanskaya St., Moscow 105005.
Competing Interests:
No
I. E. Shumskaya
City Clinical Oncology Hospital No. 1, Moscow Healthcare Department
Russian Federation
Competing Interests:
Russian Federation
17/1 Baumanskaya St., Moscow 105005.
Competing Interests:
No
G. P. Kolesnikov
Moscow City Oncology Hospital No. 62, Moscow Healthcare Department
Russian Federation
Competing Interests:
Russian Federation
27 Istra, Moscow region 143423.
Competing Interests:
No
E. S. Kuzmina
Salekhard Regional Clinical Hospital
Russian Federation
Competing Interests:
Russian Federation
39 Mira St., Salekhard 629001.
Competing Interests:
No
D. Kh. Latipova
P.A. Hertzen Moscow Oncology Research Institute — branch of the National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
3 2nd Botkinskiy Proezd, Moscow 125284.
Competing Interests:
No
E. S. Lyutova
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
11/1 Delovaya St., Nizhny Novgorod 603093.
Competing Interests:
No
M. M. Fael
City Polyclinic No. 11, Moscow Healthcare Department
Russian Federation
Competing Interests:
Russian Federation
14 Kravchenko St., Moscow 119331.
Competing Interests:
No
A. N Chugarova
Tver Regional Clinical Oncology Dispensary
Russian Federation
Competing Interests:
Russian Federation
57/37 15 let Oktyabrya St., Tver 170008.
Competing Interests:
No
A. S. Antipin
Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
Russian Federation
Competing Interests:
Russian Federation
42 Blyukhera St., Chelyabinsk 454087.
Competing Interests:
No
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For citations:
Volkova M.I., Kalpinskiy A.S., Borisov P.S., Evsyukova O.I., Olshanskaya A.S., Matveev V.B., Alekseev B.Ya., Peganova E.V., Nasretdinov A.F., Lymar E.V., Ovchinnikova E.G., Sveklina T.A., Usynin E.A., Abdelgafur A.M., Tararova E.A., Shumova L.M., Belenkov A.S., Dolgov I.Yu., Ponomareva N.G., Evstigneeva I.V., Ivanov A.N., Isaev A.R., Leonenkov R.V., Meskikh A.V., Mukhitova M.R., Orlova S.A., Teslenok I.V., Shegurova M.M., Aivazov M.T., Amoev Z.V., Babina K.G., Vorontsova A.A., Karabina E.V., Kirdakova N.V., Shumskaya I.E., Kolesnikov G.P., Kuzmina E.S., Latipova D.Kh., Lyutova E.S., Fael M.M., Chugarova A.N., Antipin A.S. 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. Cancer Urology. 2021;17(1):31-44. (In Russ.) https://doi.org/10.17650/1726-9776-2021-17-1-31-44
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