Abstract
BackgroundSequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI).MethodsA prospective observational cohort in Mexico (2012–2019). We included 132 subjects with metastatic RCC and who had progression despite treatment with sunitinib. The primary end-point was time to disease progression as evaluated every 12–16 weeks.ResultsThe mean age of the cohort was 59 years (interquartile range [IQR] 50–72), 96 (73%) were men, and 48 (36%) had a favorable prognosis according to the IMDC (International Metastatic RCC Database Consortium) prognostic model. The median progression-free survival (PFS) and overall-survival after the introduction of sorafenib treatment was 8.6 months (95% confidence interval [CI]: 6.7–10.5) and 40 months (95% CI: 34.5–45.4) respectively. The median overall survival from RCC diagnosis to death was 71 months (95% CI: 58.2–83.8). On multivariable analyses, age > 65 years was associated with a longer PFS (HR 0.51; 95% CI: 0.31–0.86; p = 0.018). The median PFS in subjects aged > 65 years was longer compared to subjects ≤65 years (14.0 [95% CI: 9.2–18.8] vs. 7.2 months [95% CI: 5.3–9.1]; p = 0.012). Adverse events grade ≥ 3 associated with sorafenib occurred in 38 (29%) patients.ConclusionSequential inhibition of VEGF with sorafenib as a second-line treatment may benefit patients with metastatic RCC, especially in subjects > 65 years old.
Highlights
Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC)
Renal cell carcinoma (RCC) is one of the most common types of cancer and its incidence has been rising by approximately 0.6% each year; death rates have been falling by 0.7% each year [1, 2]
We included 132 subjects with metastatic RCC treated by surgical resection and treated with sunitinib as the first-line treatment (Supplementary Fig. 1 includes flow chart of patients who met inclusion/exclusion criteria for the cohort study)
Summary
Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI). Patients with advanced RCC develop new metastatic lesions up to 10–. 30% despite being treated with new drugs, including vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) or targeted therapies [3, 4]. Martín-Aguilar et al BMC Cancer (2021) 21:16 line therapy, especially in patients with RCC initially treated with cytokine therapy [11, 12]. In patients with advanced RCC treated initially with sunitinib, the sequential use of a second drug with a similar molecular target could raise doubts about its clinical usefulness [13]. Retrospective observational studies have shown a lack of cross resistance between sequential use of TKIs and the distinctive toxicity spectra that occasionally permit tolerance of one TKI over another [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
