Abstract
Background
Tyrosine kinase inhibitors (TKIs) that target the vascular endothelial growth factor
receptor (VEGFR) are oral therapies used to treat metastatic renal cell carcinoma
(mRCC). VEGFR TKI treatment is often complicated by dose-limiting adverse events (AE).
We sought to describe dose intensity and clinical outcomes in a real-world cohort
of patients treated with VEGFR TKIs to better characterize dosing patterns and toxicity
management compared with previously reported clinical trials.
Materials and Methods
We conducted a retrospective chart review of sequential patients with mRCC treated
with VEGFR TKIs at one academic medical center from 2014 to 2021.
Results
139 patients (75% male, 75% white, median age 63 years) were treated with 185 VEGFR
TKIs in our real-world cohort. Per IMDC criteria, 24% had good risk, 54% intermediate
risk, and 22% poor risk mRCC. With their first VEGFR TKI, median relative dose intensity
(RDI) was 79%. 52% of patients required a dose reduction, 11% discontinued treatment
due to AEs, 15% visited the ED, and 13% were hospitalized for treatment-related adverse
events. Cabozantinib had the highest rate of dose reductions (72%) but a low rate
of discontinuation (7%). Real-world patients consistently had lower RDI than reported
clinical trials with more frequent dose reductions, fewer drug discontinuations, shorter
progression-free survival, and shorter overall survival.
Conclusion
Real-world patients were less able to tolerate VEGFR TKIs compared to patients treated
on clinical trials. Low real-world RDI, high dose reductions, and low overall discontinuation
rates can inform patient counseling prior to treatment initiation and during therapy.
Microabstract
Patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors
at a single academic medical center were retrospectively reviewed. These 139 real-world
patients had high rates of dose reduction (52%) but low rates of drug discontinuation
(11%), with lower relative dose intensity than reported in clinical trials.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Genitourinary CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Contemporary treatment of metastatic renal cell carcinoma.Med Oncol. 2018; 35: 156https://doi.org/10.1007/s12032-018-1217-1
- Systemic therapy of metastatic renal cell carcinoma: Review of the current literature.Urologia. 2019; 86: 3-8https://doi.org/10.1177/0391560318802166
- A Systematic Review of the Efficacy and Safety Experience Reported for Sorafenib in Advanced Renal Cell Carcinoma (RCC) in the Post-Approval Setting.PLoS One. 2015; 10https://doi.org/10.1371/journal.pone.0120877
- Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma.Eur Urol. 2016; 69: 345-351https://doi.org/10.1016/j.eururo.2015.07.006
- Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial.J Clin Oncol. 2017; 35: 591-597https://doi.org/10.1200/JCO.2016.70.7398
- Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.Lancet. 2011; 378: 1931-1939https://doi.org/10.1016/S0140-6736(11)61613-9
- Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial.The Lancet Oncology. 2015; 16: 1473-1482https://doi.org/10.1016/S1470-2045(15)00290-9
- Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial.The Lancet Oncology. 2016; 17: 917-927https://doi.org/10.1016/S1470-2045(16)30107-3
- Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial.The Lancet Oncology. 2020; 21: 1563-1573https://doi.org/10.1016/S1470-2045(20)30436-8
- Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study.J Clin Oncol. 2014; 32: 1412-1418https://doi.org/10.1200/JCO.2013.50.8267
- Randomized, Open-Label, Phase III Trial Of Pazopanib Versus Sunitinib In First-Line Treatment Of Patients With Metastatic Renal Cell Carcinoma (MRCC): Results of the Comparz Trial.Annals of Oncology. 2012; 23: ixe13https://doi.org/10.1016/S0923-7534(20)34325-8
- Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.N Engl J Med. 2021; 384: 1289-1300https://doi.org/10.1056/NEJMoa2035716
- Decreased relative dose intensity during the early phase of treatment impacts the therapeutic efficacy of sunitinib in metastatic renal cell carcinoma.Jpn J Clin Oncol. 2018; 48: 667-672https://doi.org/10.1093/jjco/hyy078
- A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results.Trials. 2015; 16: 495https://doi.org/10.1186/s13063-015-1023-4
- Pazopanib versus Sunitinib in Metastatic Renal-Cell Carcinoma.N Engl J Med. 2013; 369: 722-731https://doi.org/10.1056/NEJMoa1303989
- Cabozantinib use in metastatic renal cell carcinoma patients in clinical practice: Evaluation of dosing patterns, tolerability, and outcomes compared to clinical trials.J Oncol Pharm Pract. 2020; 26: 861-865https://doi.org/10.1177/1078155219875509
- Real-world evidence of cabozantinib in patients with metastatic renal cell carcinoma: Results from the CABOREAL Early Access Program.European Journal of Cancer. 2021; 142: 102-111
- Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma.The New England Journal of Medicine. 2021; 384: 829-841
- Assessing the Safety and Efficacy of Two Starting Doses of Lenvatinib Plus Everolimus in Patients with Renal Cell Carcinoma: A Randomized Phase 2 Trial.European Urology. 2022; 82: 283-292
Article info
Publication history
Accepted:
February 13,
2023
Received in revised form:
February 12,
2023
Received:
December 21,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.