Sorafenib for Older Patients With Renal Cell Carcinoma: Subset Analysis From a Randomized Trial

Abstract

BackgroundThe perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.MethodsThis retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age ≥70 years, n = 115) and younger patients (age <70 years, n = 787) who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease), time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportional hazards model. Kaplan–Meier analyses were used to summarize time-to-event data.ResultsMedian progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66) and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69). Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively) and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively). Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03) and younger patients (90 days with sorafenib vs 52 days with placebo; HR = 0.69, 95% CI = 0.59 to 0.81) and improved quality of life over that time.ConclusionsAmong patients with advanced renal cell carcinoma receiving sorafenib treatment, outcomes of older (≥70 years) and younger (<70 years) patients were similar.

Favorable Outcome in Elderly Asian Patients with Metastatic Renal Cell Carcinoma Treated with Everolimus: The Osaka Urologic Oncology Group

“…Data from clinical trials show that sorafenib reduces the risk of disease progression, compared with placebo, to the same extent in elderly patients and younger patients (Eisen et al, 2008). Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks) and older patients (26.3 weeks) (Eisen et al, 2008). It is now believed that cancer control with sorafenib is independent of age.…”

“…Many clinical trials therefore exclude older patients, particularly those with poor performance status, and few age-specific studies have been published, although evidence shows that targeted agents for mRCC are as effective and well tolerated in elderly patients as in younger patients (Porta et al, 2012). Data from clinical trials show that sorafenib reduces the risk of disease progression, compared with placebo, to the same extent in elderly patients and younger patients (Eisen et al, 2008). Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks) and older patients (26.3 weeks) (Eisen et al, 2008).…”

Risk factors and model for predicting toxicity‐related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor–targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

“…[27][28][29][30] Older age has not been shown to affect the efficacy of VEGF-targeted therapies; however, an increased incidence of toxicity in these patients has been reported. [31][32][33][34][35][36] In addition, this patient population is Figure 2. Cumulative incidence of TrTD according to risk groups, which were developed with the number of risk factors for TrTD (low, 0 or 1 risk factor; INT, 2 risk factors; high, 3 risk factors).…”

Cardiologic evaluation of patients undergoing chemoterapy

“…Anche questa nuova classe farmacologica è però gravata da un alto tasso di cardiotossicità, infatti in corso di trattamento fino all'11% dei pazienti sviluppa un evento cardiovascolare, tra cui infarto miocardico acuto e scompenso cardiaco, il 28% sviluppa una riduzione asintomatica della FE>10%, che è reversibile dopo la sospensione o la riduzione della dose del farmaco, mentre il 47% sviluppa ipertensione arteriosa [12]. Il SORAFENIB, utilizzato nella terapia del tumore renale metastatico e dell'epatocarcinoma, presenta una incidenza di disfunzione cardiaca minore rispetto al Sunitinib, anche in questo caso reversibile; nel 3% dei casi è stata osservata una sindrome coronarica acuta e il 17-43% sviluppa ipertensione [13].…”