Safety and toxicity of cabozantinib monotherapy in patients with advanced renal cell carcinoma: a Russian multicenter observational study

Maria I. Volkova; Волкова Мария Игоревна; Alexey S. Kalpinskiy; Калпинский Алексей Сергеевич; Konstantin V. Menshikov; Меньшиков Константин Викторович; Lilia V. Gorbuleva; Горбулева Лилия Викторовна; Alexander V. Sultanbaev; Султанбаев Александр Валерьевич; Olga I. Evsyukova; Евсюкова Ольга Игоревна; Varazdat R. Meltonian; Мелтонян Вараздат Рубенович; Sergey V. Mishugin; Мишугин Сергей Владимирович; Mikhail R. Maturov; Матуров Михаил Ринатович; Anna S. Olshanskaya; Ольшанская Анна Сергеевна; Dmitrii Iu. Shemetov; Шеметов Дмитрий Юрьевич; Tatyana A. Sannikova; Санникова Татьяна Александровна; Mariia V. Makhnutina; Махнутина Мария Валерьевна; Marina A. Filipieva; Филипьева Марина Александровна; Elena A. Gaijsina; Гайсина Елена Александровна; Elena G. Ovchinnikova; Овчинникова Елена Георгиевна; Ovsep A. Mailian; Маилян Овсеп Араратович; Boris Ya. Alekseev; Алексеев Борис Яковлевич; Vsevolod B. Matveev; Матвеев Всеволод Борисович

doi:10.26442/18151434.2023.2.202262

Safety and toxicity of cabozantinib monotherapy in patients with advanced renal cell carcinoma: a Russian multicenter observational study

作者: Volkova M.¹^,2, Kalpinskiy A.³, Menshikov K.⁴^,5, Gorbuleva L.⁶, Sultanbaev A.⁴, Evsyukova O.⁷, Meltonian V.⁸, Mishugin S.⁹, Maturov M.⁹, Olshanskaya A.¹, Shemetov D.¹⁰, Sannikova T.¹¹, Makhnutina M.¹², Filipieva M.¹¹, Gaijsina E.¹³^,14, Ovchinnikova E.¹⁵, Mailian O.³, Alekseev B.³^,16, Matveev V.⁷
隶属关系:
1. City Clinical Oncology Hospital №1
2. Russian Medical Academy of Continuous Professional Education
3. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre
4. Republican Clinical Oncology Dispensary
5. Bashkir State Medical University
6. Efetov Crimean Republican Oncological Clinical Dispensary
7. Blokhin National Medical Research Center of Oncology
8. Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)
9. Pletnev City Clinical Hospital
10. Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine
11. Perm Regional Oncological Dispensary
12. Samara Regional Clinical Oncology Dispensary
13. Tyumen State Medical University
14. Multidisciplinary Clinical Medical Center "Medical City"
15. Nizhny Novgorod Regional Clinical Oncology Dispensary
16. Russian Biotechnological University
期: 卷 25, 编号 2 (2023)
页面: 221-228
栏目: CLINICAL ONCOLOGY
URL: https://journals.rcsi.science/1815-1434/article/view/132821
DOI: https://doi.org/10.26442/18151434.2023.2.202262
ID: 132821

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Aim. To assess the safety and to analyze an influence of cabozantinib monotherapy toxicity on treatment efficacy in unselected Russian patients with metastatic renal cell carcinoma (mRCC).

Materials and methods. Medical data of 92 patients with verified mRCC were included in the study. The median age of the patients was 56 (19–79) years, most of them - 60 (65.2%) were of male gender. Twenty five (27.2%) persons had Eastern Cooperative Oncology Group performance status (ECOG PS). At the time of cabozantinib monotherapy start 5 (5.4%) patients had favorable, 54 (58.7%) – intermediate, and 33 (35.9%) – unfavorable prognosis by International Metastatic Renal Cancer Database Consortium (IMDC) model. Eighty-three (90.2%) patients were pretreated, including 76 (82.6%) patients who previously received anti-angiogenic agents. All patients were administered with cabozantinib monotherapy (60 mg/day); dose adjustment was performed according to the instruction.

Results. Adverse events (AEs) were reported in 81 (88.0%) of 92 patients; 30 (32.6%) AEs were grade 3–4. Toxicity-related dose reduction of cabozantinib was required in 28 (30.4%), treatment interruption in 15 (16.3%), and discontinuation in 2 (2.2%) patients. The most common AEs were hypertension (69 patients, 75.0%), asthenia (47 patients, 51.1%), diarrhea (43 patients, 46.7%), and palmar-plantar erythrodysesthesia (43 patients, 46.7%). The most common severe AEs were: arterial hypertension (17 patients, 18.5%), diarrhea (6 patients, 6.5%), and palmar-plantar erythrodysesthesia (2 patients, 2.2%). The most frequent laboratory abnormalities during therapy were elevated serum transaminases (33 patients, 35.9%), anemia (13 patients, 14.1%), and thrombocytopenia (10 patients, 10.9%). No previously unreported AEs or laboratory abnormalities were observed. There was a significant increase in progression-free survival (hazard ratio 2.5; 95% confidence interval 1.0–5.9; p=0.046) and overall survival (hazard ratio 3.0; 95% confidence interval 1.2–8.3; p<0.025) in patients with treatment-related arterial hypertension.

Conclusion. The observational study confirmed the acceptable safety profile of cabozantinib in the first and subsequent lines of treatment in mRCC patients. No new safety signals were identified. Treatment-related arterial hypertension may be a favorable predictor of survival.

关键词

renal cell carcinoma, cabozantinib, safety, toxicity, hypertension

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作者简介

Maria Volkova

City Clinical Oncology Hospital №1; Russian Medical Academy of Continuous Professional Education

编辑信件的主要联系方式.
Email: mivolkova6@gmail.com
ORCID iD: 0000-0001-7754-6624

D. Sci. (Med.), Professor

俄罗斯联邦, Moscow; Moscow

Alexey Kalpinskiy

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre

Email: mivolkova6@gmail.com
ORCID iD: 0000-0002-2209-3020

Cand. Sci. (Med.)

俄罗斯联邦, Moscow

Konstantin Menshikov

Republican Clinical Oncology Dispensary; Bashkir State Medical University

Email: kmenshikov80@bk.ru
ORCID iD: 0000-0003-3734-2779

Cand. Sci. (Med.), assistant professor

俄罗斯联邦, Ufa; Ufa

Lilia Gorbuleva

Efetov Crimean Republican Oncological Clinical Dispensary

Email: mivolkova6@gmail.com
ORCID iD: 0009-0001-3991-3881

Oncologist, Chemotherapist

俄罗斯联邦, Simferopol

Alexander Sultanbaev

Republican Clinical Oncology Dispensary

Email: mivolkova6@gmail.com
ORCID iD: 0000-0003-0996-5995

Cand. Sci. (Med.)

俄罗斯联邦, Ufa

Olga Evsyukova

Blokhin National Medical Research Center of Oncology

Email: mivolkova6@gmail.com
ORCID iD: 0000-0002-3016-6357

Oncologist

俄罗斯联邦, Moscow

Varazdat Meltonian

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

Email: mivolkova6@gmail.com
ORCID iD: 0009-0008-7636-3365

Oncourologist

俄罗斯联邦, Saint Petersburg

Sergey Mishugin

Pletnev City Clinical Hospital

Email: mivolkova6@gmail.com
ORCID iD: 0009-0007-0907-4937

Cand. Sci. (Med.), Pletnev City Clinical Hospital

俄罗斯联邦, Moscow

Mikhail Maturov

Pletnev City Clinical Hospital

Email: mivolkova6@gmail.com
ORCID iD: 0009-0000-6177-7794

Oncologist, Oncourologist

俄罗斯联邦, Moscow

Anna Olshanskaya

City Clinical Oncology Hospital №1

Email: mivolkova6@gmail.com
ORCID iD: 0000-0003-0389-564X

Cand. Sci. (Med.)

俄罗斯联邦, Moscow

Dmitrii Shemetov

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

Email: mivolkova6@gmail.com
ORCID iD: 0009-0009-4370-6218

Department Head, Oncologist

俄罗斯联邦, Chelyabinsk

Tatyana Sannikova

Perm Regional Oncological Dispensary

Email: mivolkova6@gmail.com
ORCID iD: 0009-0002-6328-7785

Department Head, Oncologist

俄罗斯联邦, Perm

Mariia Makhnutina

Samara Regional Clinical Oncology Dispensary

Email: mivolkova6@gmail.com

Oncologist

俄罗斯联邦, Samara

Marina Filipieva

Perm Regional Oncological Dispensary

Email: mivolkova6@gmail.com

Oncologist

俄罗斯联邦, Perm

Elena Gaijsina

Tyumen State Medical University; Multidisciplinary Clinical Medical Center "Medical City"

Email: mivolkova6@gmail.com

Cand. Sci. (Med.)

俄罗斯联邦, Tyumen; Tyumen

Elena Ovchinnikova

Nizhny Novgorod Regional Clinical Oncology Dispensary

Email: mivolkova6@gmail.com
ORCID iD: 0000-0002-9254-8916

Cand. Sci. (Med.)

俄罗斯联邦, Nizhny Novgorod

Ovsep Mailian

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre

Email: mivolkova6@gmail.com

Cand. Sci. (Med.)

俄罗斯联邦, Moscow

Boris Alekseev

Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre; Russian Biotechnological University

Email: mivolkova6@gmail.com

D. Sci. (Med.), Prof.

俄罗斯联邦, Moscow; Moscow

Vsevolod Matveev

Blokhin National Medical Research Center of Oncology

Email: mivolkova6@gmail.com
ORCID iD: 0000-0001-7748-9527

D. Sci. (Med.), Prof., Corr. Memb. RAS

俄罗斯联邦, Moscow

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