Sorafenib tolerability in elderly patients with advanced renal cell carcinoma: results from a large pooled analysis

Abstract

Background:Elderly patients tend to be underrepresented in renal cell carcinoma (RCC) clinical trials. The Sorafenib RCC Integrated Database includes data from six clinical trials and two expanded-access studies evaluating sorafenib monotherapy in >4600 patients with RCC. Using this database, sorafenib tolerability and treatment patterns were analysed according to age group (<55, 55–<65, 65–<75, or ⩾75 years).Methods:Dosing patterns, and incidence, prevalence and cumulative incidence of drug-related adverse events (DRAEs) and fatal DRAEs were assessed.Results:Overall, 4684 patients were evaluable (<55 years, n=1126; 55–<65, n=1579; 65–<75, n=1382; ⩾75, n=559). Treatment patterns were generally similar across subgroups, although sorafenib treatment duration was ∼30% shorter in the ⩾75-years subgroup. There were no substantial differences in any-grade DRAEs with sorafenib between subgroups. Drug-related adverse events and dose modifications due to DRAEs tended to occur in months 0–3 and declined thereafter; there was no evidence of cumulative toxicity. Fatal DRAEs were rare (0.7% overall; 95% confidence interval, 0.5–1.0%).Conclusion:Sorafenib was well tolerated regardless of age in a heterogeneous population of RCC patients.

SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer

“…AEs were generally less frequent during second-line than first-line therapy. Although the precise reasons are not known, this observation is consistent with previous data showing that AEs tend to occur early in the course of TKI therapy [32,33], and suggests possible cross-tolerance and adaptation to TKI treatment. Prospective assessment of cardiac safety (LVEF and NT-proBNP values) was included in the protocol following previous reports of cardiotoxicity and reduced LVEF, particularly with sunitinib [30,[34][35][36][37][38].…”

Does dose modification affect efficacy of first-line pazopanib in metastatic renal cell carcinoma?

“…The most common AEs observed in our study were fatigue (33.3%), nausea (17.4%), diarrhea (16%), and hypertension (13%), which is consistent with data in the literature [2]. Treatment duration and toxicity data from real-world experience with sunitinib and sorafenib show that, overall, about half of patients require a dose reduction of sunitinib [13] and sorafenib [14,15] because of toxicity; however, no similar data are yet available for pazopanib. The disease control rate (DCR) in our report (n = 20; 29%) is slightly lower than that reported in the literature, but it raised significantly when considering the DCR reported in group 1 (44%).…”

Sorafenib Treatment of Advanced Renal Cell Carcinoma Patients in Daily Practice: The Large International PREDICT Study

“…The sorafenib DRAE profile was further analyzed using a large pooled integrated database of 4684 patients who were receiving sorafenib monotherapy for advanced RCC. 32 This analysis of 8 company-sponsored phase I to III clinical studies, including TARGET, NA-ARCCS, and EU-ARCCS, demonstrated that DRAEs typically occurred during the first 3 months and declined thereafter. Although the PREDICT study included a broader patient population than the clinical trials, no unexpected AEs were observed compared with the analysis of the pooled integrated database.…”