Effects and Side Effects of Using Sorafenib and Sunitinib in the Treatment of Metastatic Renal Cell Carcinoma
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Abstract:
In recent years, targeted therapies have proven beneficial in terms of progression-free survival (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC). The tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib are included in international clinical guidelines as first-line and second-line therapy in mRCC. Hypertension is an adverse effect of these drugs and the degree of hypertension associates with the anti-tumour effect. Studies have compared newer targeted drugs to sorafenib and sunitinib in terms of PFS, OS, quality of life and safety profiles. Phase III studies presented promising response rates and acceptable safety profiles of axitinib and tivozanib compared to sorafenib, and a phase II study reported greater efficacy using a combination of bevacizumab and IFN-α compared to sunitinib. Treatment with nintedanib exhibited a notably low prevalence of hypertension compared to sunitinib. The use of sorafenib and sunitinib are challenged by new drugs, but do not appear likely to be substituted in the near future. To clarify whether newer targeted drugs should replace sorafenib and sunitinib, more research is needed. This manuscript reviews the current utility and adverse effects of sorafenib and sunitinib and newer targeted therapies in the treatment of mRCC.Keywords:
Axitinib
Pazopanib
Targeted Therapy
495 Background: Axitinib has been approved for 2nd line treatment in the UK for patients with advanced renal cell carcinoma on the basis of the AXIS study, which showed improved progression free survival (PFS) and a trend towards overall survival (OS) benefit. There is no randomised data to support the use of Axitinib after first line Pazopanib. Hence, we compared the efficacy of Axitinib after first line Pazopanib or Sunitinib. The influence of Heng prognostic risk score (HPRS) at initiation of Axitinib, previous nephrectomy, and haemoglobin (Hb) rise during Axitinib treatment on outcome was also evaluated. Methods: Thirty one patients were commenced on Axitinib between May 2013-May 2016. Patient demographics, laboratory parameters, and survival data were collected retrospectively. Data were analysed in October 2016, which served as a censor date for patients who were alive. Analysis of PFS and OS was performed by Kaplan-Meier estimates and log-rank test. Results: All 31 patients received axitinib as 2nd line treatment. At the time of analysis, 14 patients were alive and 7 remained on axitinib. The prognostic factors influencing outcome are shown in the table. Conclusions: There was no significant difference in PFS or OS regardless of first line treatment, supporting the use of axitinib post pazopanib or sunitinib. Prior nephrectomy, and favourable HPRS significantly predict better PFS and OS. The impact of Hb rise needs further validation in a larger cohort.[Table: see text]
Axitinib
Pazopanib
Demographics
Log-rank test
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609 Background: Axitinib is licensed in Europe for the treatment of adult patients with advanced renal cell carcinoma after failure of sunitinib, but not pazopanib. Efficacy is based on the AXIS trial which reported a progression free survival (PFS) of 4.8 months and an overall survival (OS) of 15.2 months in patients who had received prior sunitinib. Despite widespread use of pazopanib in the first line setting there is no randomised trial evidence to support the use of axitinib after pazopanib. The Beatson Cancer Centre (BCC) renal cancer clinic provides all systemic therapy for a population of 2.8 million. Within BCC axitinib is used post sunitinib or pazopanib. We performed an analysis of patient outcomes in patients who commenced axitinib in WOS between November 2013 and November 2014. Methods: Data were collected prospectively from the electronic clinical records. Duration of treatment was used as a surrogate for progression free survival (PFS). Data were analysed in April 2015 which served as the censor date for those still alive. Results: 46 patients were included. At the time of analysis 38 patients had stopped axitinib and 30 patients had died. 22 patients (48%) had received prior pazopanib and 21 (46%) prior sunitinib. For the patients who received axitinib in the 2 nd line setting (n = 38) median duration of treatment was 4.8 months (95% CI 0.55 – 9.12). Median duration post sunitinib and pazopanib was 4.8 months (95% CI 0 – 9.7) and 5.3 months (95% CI 2.2- 8.4). Median OS was 9.2 months (95% CI 6.44 – 12.05) overall and 9.44 months (95% CI 5.36 – 13.5) and 8.36 months (95% CI 1.7 – 11.6) post sunitinib and pazopanib respectively. Conclusions: PFS appears to be comparable to reported trial data irrespective of first line treatment indicating similar efficacy and tolerability in real life. We found no evidence of a significant difference in OS regardless of first line treatment which supports the current practice of using axitinib post sunitinib or pazopanib. The inferior OS compared to AXIS trial could be multifactorial and requires further investigation.
Pazopanib
Axitinib
Progression-free survival
Kidney cancer
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Tyrosine kinase inhibitors such as sorafenib and axitinib were developed to treat malignancies, including stage IV renal cell carcinoma. Recently, we experienced a patient with pancreatic side effects from both sorafenib and axitinib. We report this case and include a discussion of the literature.
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Pancreatic carcinoma
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Pazopanib
Post-hoc analysis
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Background: Sunitinib and pazopanib are tyrosine kinase inhibitors (TKIs) used as first-line therapy for metastatic renal cell carcinoma (mRCC). In this study, our objective was to evaluate the effectiveness of sunitinib or pazopanib in patients with intermediate or poor risk metastatic renal cell carcinoma. Methods: A total of 60 patients with metastatic renal cell carcinoma were retrospectively evaluated between January 2014 and December 2020. Survival analyzes were performed with the Kaplan-Meier and log-rank tests. Results: Forty-six (76.7%) patients were male. Of the patients who received sunitinib, 22 patients (57.9%) were in the intermediate risk group, while 16 patients (42.1%) were in the poor risk group. Among patients receiving pazopanib, 14 patients (63.6%) were in the intermediate-risk group, while 8 patients (36.4%) were in the poor-risk group. There were no significant difference in the intermediate risk group of patients in terms of median progression-free survival between sunitinib and pazopanib (p=0.742). No significant differences were found in terms of progression-free survival in the high-risk group of patients (p=0.254). There were no significant differences in overall survival in the intermediate-risk group of patients receiving sunitinib or pazopanib (p = 0.377). There were no significant differences in terms of overall survival in the high-risk patient group receiving sunitinib or pazopanib (p = 0.3777). Conclusions: There were no significant difference in terms of progression-free survival and overall survival between the intermediate and poor-risk patient groups receiving pazopanib or sunitinib.
Pazopanib
Progression-free survival
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Pazopanib
Clinical Practice
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Abstract Background: Sunitinib and pazopanib are orally-administered tyrosine kinase receptor inhibitors (TKIs) approved as first-line therapy for the treatment of metastatic renal cell carcinoma (mRCC). The IMDC criteria are a predictive prognostic model for patients with mRCC when stratified into three prognosis groups: favourable, intermediate and poor. We retrospectively compared the efficacy and safety of sunitinib and pazopanib as first-line therapy for patients with mRCC in our single institution database. Methods: Retrospective analysis was done to compare progression-free survival (PFS) and side effects of sunitinib and pazopanib as first-line therapy in patients with mRCC. Patients were stratified into prognosis groups according to IMDC criteria. Disease assessment was performed on measurable aspects of disease based on computed tomography or magnetic resonance imaging reports. Survival analysis was performed using the Kaplan-Meier method and Cox regression, with disease progression as the endpoint. Results: Data was obtained from 228 patients with mRCC who were treated with either pazopanib (n=57) or sunitinib (n=171). No significant difference in PFS was found between sunitinib and pazopanib (HR for disease progression or all-cause death, 1.10; 95%CI: 0.76-1.57, p=0.62). Median PFS time for patients receiving sunitinib was 9.4 months and for pazopanib, 8.5 months. Median PFS for patients with intermediate-risk disease was similar between groups (9.4 months vs. 9.2 months, respectively, p=0.93). However, patients treated with sunitinib experienced a greater number of side effects compared to pazopanib. Conclusions : Sunitinib and pazopanib are similarly efficacious as first-line therapy for mRCC. However, adverse events are lower with pazopanib.
Pazopanib
Clinical endpoint
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