Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM

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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.

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

Department of Urology

24 Kashirskoe Shosse, Moscow 115478

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

M. T. Aivazov

Oncology Center No. 4, Moscow Department of Health

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

P. S. Borisov

City Clinical Oncology Dispensary

ORCID iD: 0000-0003-4267-2799

3/5 2nd Berezovya alleya, Saint Petersburg 197022

Russian Federation

A. A. Vorontsovа

Oncology Center No. 4, Moscow Department of Health

7 Medikov St., Moscow 115304

Russian Federation

I. V. Evstigneeva

Tver Regional Clinical Oncology Dispensary

57/37 15 let Oktyabrya St., Tver 170008

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

Department of Urology

24 Kashirskoe Shosse, Moscow 115478

Russian Federation

O. V. Zhelezin

Nizhny Novgorod Regional Clinical Oncology Dispensary

11/1 Delovaya St., Nizhny Novgorod 603093

Russian Federation

A. S. Kalpinsky

Р. 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

E. V. Karabina

Tula Regional Oncology Dispensary

ORCID iD: 0000-0001-6062-5318

201A Plekhanova St., Tula 300040

N. V. Kirdakova

City Clinical Oncology Hospital No. 1, Moscow Department of Health

ORCID iD: 0000-0001-8233-9224

17/1 Baumanskaya St., Moscow 105005

G. P. Kolesnikov

Moscow City Oncology Hospital No. 62, Department of Health of Moscow

ORCID iD: 0000-0002-1272-9136

27 Istra, Moscow region 143423

E. S. Kuzmina

Salekhard Regional Clinical Hospital

ORCID iD: 0000-0001-8979-2208

39 Mira St., Salekhard 629001

D. Kh. Latipova

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

ORCID iD: 0000-0002-8906-0370

68 Leningradskaya St., Pesochny, Saint Petersburg 197758

R. V. Leonenkov

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

ORCID iD: 0000-0001-9710-2406

68A Leningradskaya St., Pesochny, Saint Petersburg 197758

M. R. Maturov

D.D. Pletnev City Clinical Hospital, Moscow Department of Health

ORCID iD: 0000-0002-2455-9058

32 11th Parkovaya St., Moscow 105077

A. V. Meskikh

D.D. Pletnev City Clinical Hospital, Moscow Department of Health

32 11th Parkovaya St., Moscow 105077

S. V. Mishugin

D.D. Pletnev City Clinical Hospital, Moscow Department of Health

ORCID iD: 0000-0003-2757-1922

32 11th Parkovaya St., Moscow 105077

E. G. Ovchinnikova

Nizhny Novgorod Regional Clinical Oncology Dispensary

ORCID iD: 0000-0002-9254-8916

11/1 Delovaya St., Nizhny Novgorod 603093

A. S. Olshanskaya

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

ORCID iD: 0000-0003-0389-564X

Department of Urology

24 Kashirskoe Shosse, Moscow 115478

S. A. Protsenko

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

68 Leningradskaya St., Pesochny, Saint Petersburg 197758

T. Yu. Semiglazova

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

ORCID iD: 0000-0002-4305-6691

68 Leningradskaya St., Pesochny, Saint Petersburg 197758

R. V. Smirnov

Vologda Regional Oncology Center

ORCID iD: 0000-0002-3728-1796

100 Sovetskiy Prospekt, Vologda 160012

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

M. M. Fael

City Polyclinic No. 11, Moscow Department of Health

ORCID iD: 0000-0001-7588-665X

14 Kravchenko St., Moscow 119331

E. M. Cherniakova

Republican Oncology Dispensary Center

ORCID iD: 0000-0003-0716-8562

5 Lososinskoe Shosse, Petrozavodsk 185002

I. E. Shumskaya

City Clinical Oncology Hospital No. 1, Moscow Department of Health

201A Plekhanova St., Tula 300040

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