Sorafenib for Older Patients With Renal Cell Carcinoma: Subset Analysis From a Randomized Trial (original) (raw)
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British journal of cancer, 2013
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). Dosing patterns, and incidence, prevalence and cumulative incidence of drug-related adverse events (DRAEs) and fatal DRAEs were assessed. 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 an...
Sorafenib for the Treatment of Advanced Renal Cell Carcinoma
Clinical Cancer Research, 2006
Purpose: This report describes the U.S. Food and Drug Administration (FDA) review and approval of sorafenib (Nexavar, BAY43-9006), a new small-molecule, oral, multi-kinase inhibitor for the treatment of patients with advanced renal cell carcinoma (RCC). Experimental Design: After meeting with sponsors during development studies of sorafenib, the FDA reviewed the phase 3 protocol under the Special Protocol Assessment mechanism. Following new drug application submission, FDA independently analyzed the results of two studies in advanced RCC: a large, randomized, double-blinded, phase 3 international trial of single-agent sorafenib and a supportive phase 2 study. Results: In the phase 3 trial, 902 patients with advanced progressive RCC after one prior systemic therapy were randomized to 400 mg sorafenib twice daily plus best supportive care or to a matching placebo plus best supportive care. Primary study end points included overall survival and progression-free survival (PFS). A PFS an...
Experience with sorafenib in the treatment of advanced renal cell carcinoma
Therapeutic Advances in Urology, 2012
The molecular-targeted agent sorafenib is the first anticancer agent able to slow the progression of advanced/metastatic renal cell carcinoma, a tumor that was formerly refractory to conventional therapy. Experience from everyday clinical practice and investigations exploring the suitability of this agent for patients with harmful pathological conditions has extended the use of sorafenib to other settings of renal cell carcinoma and to particular risk populations. The aim of this review is to provide evidence on the most effective and safe use of sorafenib. The review pays particular attention to patients who have several comorbidities, such as impaired renal and cardiac function, and older patients whose frailty due to impaired organ function necessitates the most careful administration of targeted antineoplastic agents.
Efficacy of Targeted Therapy for Metastatic Renal Cell Carcinoma in the Elderly Patient Population
Clinical Genitourinary Cancer, 2014
Targeted therapy has become the mainstay of treatment for metastatic renal cell carcinoma (mRCC), and the efficacy of this therapy in the older population is poorly understood. Data from 1381 patients with mRCC treated with first-line anti-vascular endothelial growth factor (VEGF) therapy were collected through the International mRCC Database Consortium from 12 centers. When adjusted for poor prognostic factors, age 75 years and older was not found to be associated with poorer overall survival or shorter treatment duration. This suggests that advanced age alone should not preclude a patient from targeted therapy. Introduction/Background: Targeted therapy has become the mainstay of treatment for mRCC. The efficacy of this therapy in the older population is poorly understood. Patients and Methods: Data from patients with mRCC treated with first-line anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers. Patient characteristics, data on second-line therapy, and outcomes including treatment duration and overall survival, were evaluated using summary statistics and multivariate analysis. Results: All patients (n ¼ 1381) were treated with front-line targeted therapy; 144 (10%) were 75 years old or older. Six patients (4%) were favorable risk, 99 patients (69%) intermediate risk, and 39 patients (27%) poor risk according to Heng Journal of Clinical Oncology 2009 prognostic factors. The initial treatment for those 75 years of age was sunitinib (n ¼ 98), sorafenib (n ¼ 35), bevacizumab (n ¼ 7), and AZD217 (n ¼ 4). Twenty-three percent of older patients and 39% of the younger patients went on to receive second-line therapy (P < .0001). The overall response rate, median treatment duration, and overall survival for the older versus younger group were 18% versus 25% (P ¼ .0975), 5.5 months versus 7.5 months (P ¼ .1388), and 16.8 months versus 19.7 months (P ¼ .3321), respectively. When adjusted for poor prognostic factors, age 75 years and older was not found to be associated with poorer overall survival (hazard ratio [HR], 1.002; 95% confidence interval [CI], 0.781-1.285) or shorter treatment duration (HR, 1.018; 95% CI, 0.827-1.252). The retrospective study design was the primary limitation. Conclusion: The use of advanced age as a selection criterion for targeted therapy requires further study, with data suggesting no clinically meaningful differences in overall response rate, treatment duration, and overall survival between older and younger age groups.
Clinical experience and critical evaluation of the role of sorafenib in renal cell carcinoma
Open Access Journal of Urology
Renal cell carcinoma (RCC) is a common malignancy worldwide with approximately 95,000 new cases per year and ranks as the sixth cause of cancer deaths. Until recently, the slightly active and very toxic cytokines were available for patients with advanced RCC. Advances have been made in understanding the molecular biology of renal cancer. The introduction of targeted agents has led to promising possibilities for treating these highly vascularized tumors. Angiogenesis inhibition is likely to represent the main potential therapeutic target. Sorafenib is an oral multikinase inhibitor with activity against tyrosine kinase receptors that are responsible for blood vessel development and has shown to be active in treating advanced RCC. In this review, we summarize the pharmacology, mode of action, pharmacokinetics, and safety of sorafenib use in therapy for advanced RCC.
Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma
New England Journal of Medicine, 2007
Background We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma. Methods From November 2003 to March 2005, we randomly assigned 903 patients with renalcell carcinoma that was resistant to standard therapy to receive either continuous treatment with oral sorafenib (at a dose of 400 mg twice daily) or placebo; 451 patients received sorafenib and 452 received placebo. The primary end point was overall survival. A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo. Consequently, crossover was permitted from placebo to sorafenib, beginning in May 2005. Results At the January 2005 cutoff, the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group (hazard ratio for disease progression in the sorafenib group, 0.44; 95% confidence interval [CI], 0.35 to 0.55; P<0.01). The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death, as compared with placebo (hazard ratio, 0.72; 95% CI, 0.54 to 0.94; P = 0.02), although this benefit was not statistically significant according to the O'Brien-Fleming threshold. Partial responses were reported as the best response in 10% of patients receiving sorafenib and in 2% of those receiving placebo (P<0.001). Diarrhea, rash, fatigue, and hand-foot skin reactions were the most common adverse events associated with sorafenib. Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo. Conclusions As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects.
Major response with sorafenib in advanced renal cell carcinoma after 14 years of follow-up
World Journal of Surgical Oncology, 2013
Tyrosine kinase inhibitors have dramatically improved the prognosis of metastatic renal cell carcinoma (RCC). However, it remains unknown whether treatment should be continued until progression or discontinued in patients with good response. We present the history of a woman diagnosed with RCC in 1997, who started sorafenib in 2004, two years after the occurrence of lung and mediastinal metastases. Over the following 8 years, the sorafenib dose was reduced at least 3 times due to toxicity and the treatment was discontinued twice upon the patient’s decision, from May 2005 to March 2009, then from January 2011 to August 2011. The last evaluation in January 2013 showed stable disease. This case illustrates the feasibility of treatment discontinuation without negative impact on survival, as previously shown by some authors.
Journal of Clinical Oncology, 2006
Purpose This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma. Patients and Methods Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with ≥ 25% tumor shrinkage continued open-label sorafenib; patients with ≥ 25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib. Results Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of ≥ 25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafen...