Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM
https://doi.org/10.17650/1726-9776-2019-15-3-56-69
Abstract
Objective: an assessment of efficacy and safety of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) progressed during or following ≥1 line of antiangiogenic targeted therapy.
Material. Russian multicenter observational study ROSLERCM included 73 consecutive patients with morphologically verified mRCC progressed during or following ≥1 line of antiangiogenic targeted therapy, treated with lenvatinib (18 mg/d) and everolimus (5 mg/d) in 20 Russian centers. Median age of the patients was 59 (23–73) years, a male-to-female ratio – 3:1. Most common histological type of kidney cancer was clear-cell RCC (71 (95.8 %)). More than 2 lines of previous therapy were administered in 45 (61.6 %) cases. Most patients were diagnosed with multiple metastases (71 (97.3 %)) in >1 site (61 (83.6 %)). Nephrectomy was performed in 87.7 % (64/73) of cases. At the combined therapy start ECOG PS 2–4 was registered in 16 (20.5 %), poor prognosis according to IMDC score – in 33 (45.2 %) patients. Median follow-up was 9.7 (1–26) months.
Results. Median progression-free survival achieved 16.9 (95 % confidence intervals (CI) 12.1–20.6), overall survival – 20.8 (95 % CI 15.7–25.9) months. Objective response rate was 11 % (8/73); tumor control was reached in 93.2 % (68/73) of cases. Median objective response duration was 10.5 (4.3–16.8) months, tumor control duration – 10.0 (2.5–17.5) months. Any adverse events developed in 83.6 % (61/73), adverse events grade III–V – in 23.3 % (17/73) of cases. Most frequent AE grade III–IV were diarrhea (10 (13.6 %)) and arterial hypertension (6 (8.2 %)). Unacceptable toxicity demanded treatment cancellation in 4.2 % (3/73), therapy interruption – in 30.1 % (22/73) and dose reduction – in 32.9 % (24/73) of patients.
Conclusion. Unselected mRCC patients administered with combined targeted therapy in the real world practice were registered with similar survival, lower objective response rate, and better tolerability comparing with population assigned for lenvatinib plus everolimus in the randomized phase II trial.
Keywords
About the Authors
M. I. VolkovaRussian Federation
Department of Urology
24 Kashirskoe Shosse, Moscow 115478
A. M. Abdelgafur
Russian Federation
31 Gladkova St., Cheboksary 428020, Republic of Chuvashia
M. T. Aivazov
Russian Federation
7 Medikov St., Moscow 115304
Z. V. Amoev
Russian Federation
2 Nizhnevolzhskaya Naberezhnaya, Nizhny Novgorod 603001
K. G. Babina
Russian Federation
78 im. Zemlyachki St., Volgograd 400138
P. S. Borisov
Russian Federation
3/5 2nd Berezovya alleya, Saint Petersburg 197022
A. A. Vorontsovа
Russian Federation
7 Medikov St., Moscow 115304
I. V. Evstigneeva
Russian Federation
57/37 15 let Oktyabrya St., Tver 170008
O. I. Evsyukova
Russian Federation
Department of Urology
24 Kashirskoe Shosse, Moscow 115478
O. V. Zhelezin
Russian Federation
11/1 Delovaya St., Nizhny Novgorod 603093
A. S. Kalpinsky
Russian Federation
3 2nd Botkinskiy Proezd, Moscow 125284
E. V. Karabina
201A Plekhanova St., Tula 300040
N. V. Kirdakova
17/1 Baumanskaya St., Moscow 105005
G. P. Kolesnikov
27 Istra, Moscow region 143423
E. S. Kuzmina
39 Mira St., Salekhard 629001
D. Kh. Latipova
68 Leningradskaya St., Pesochny, Saint Petersburg 197758
R. V. Leonenkov
68A Leningradskaya St., Pesochny, Saint Petersburg 197758
M. R. Maturov
32 11th Parkovaya St., Moscow 105077
A. V. Meskikh
32 11th Parkovaya St., Moscow 105077
S. V. Mishugin
32 11th Parkovaya St., Moscow 105077
E. G. Ovchinnikova
11/1 Delovaya St., Nizhny Novgorod 603093
A. S. Olshanskaya
Department of Urology
24 Kashirskoe Shosse, Moscow 115478
S. A. Protsenko
68 Leningradskaya St., Pesochny, Saint Petersburg 197758
T. Yu. Semiglazova
68 Leningradskaya St., Pesochny, Saint Petersburg 197758
R. V. Smirnov
100 Sovetskiy Prospekt, Vologda 160012
E. A. Usynin
5 Kooperativny Pereulok, Tomsk 634009
M. M. Fael
14 Kravchenko St., Moscow 119331
E. M. Cherniakova
5 Lososinskoe Shosse, Petrozavodsk 185002
I. E. Shumskaya
201A Plekhanova St., Tula 300040
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Review
For citations:
Volkova M.I., Abdelgafur A.M., Aivazov M.T., Amoev Z.V., Babina K.G., Borisov P.S., Vorontsovа A.A., Evstigneeva I.V., Evsyukova O.I., Zhelezin O.V., Kalpinsky A.S., Karabina E.V., Kirdakova N.V., Kolesnikov G.P., Kuzmina E.S., Latipova D.Kh., Leonenkov R.V., Maturov M.R., Meskikh A.V., Mishugin S.V., Ovchinnikova E.G., Olshanskaya A.S., Protsenko S.A., Semiglazova T.Yu., Smirnov R.V., Usynin E.A., Fael M.M., Cherniakova E.M., Shumskaya I.E. Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM. Cancer Urology. 2019;15(3):56-69. (In Russ.) https://doi.org/10.17650/1726-9776-2019-15-3-56-69