Factors associated with outcome in patients with advanced renal cell carcinoma in the era of antiangiogenic agents

Known clinical factors associated with outcome in advanced renal cell carcinoma (RCC) include performance status, disease-free interval, number of metastatic sites, and several laboratory variables such as hemoglobin, calcium, and lactate dehydrogenase. These factors were pertinent to the era of immunotherapy. Recent analysis from trials with anti-VEGF agents shows these factors continue to be of major importance. Additionally, several serum and molecular markers, many of which relate to certain alterations of the von Hippel-Lindau (VHL) pathway, are currently being investigated. Responses to VEGF-targeted agents seem to be related to a greater modulation of serum VEGF and soluble VEGF receptors levels. The impact of VHL gene status on clinical objective response to VEGF-targeted therapy was tested in a large study but was not found to predict a higher response rate to these agents. However, subsets of VHL mutations that predict a truncation of the VHL protein seem to have the best responses to these agents. Future prognostic models will incorporate molecular markers with clinical variables to refine prognosis and prediction in patients with metastatic clear-cell RCC treated with novel antiangiogenic agents. These models, if externally and prospectively validated, will rationally select patients for specific VEGF-directed therapeutic agents.     

Nomogram to Assess the Survival Benefit of New Salvage Agents for Metastatic Urothelial Carcinoma in the Era of Immunotherapy

Introduction

Optimal end points in phase 2 trials evaluating salvage therapy for metastatic urothelial carcinoma are necessary to identify promising drugs, particularly immunotherapeutics, where response and progression-free survival may be unreliable. We developed a nomogram using data from phase 2 trials of historical agents to estimate the 12-month overall survival (OS) for patients to which observed survival of nonrandomized data sets receiving immunotherapies could be compared.

Predictors,utilization patterns,and overall survival of patients undergoing metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy

Introduction

Metastasectomy (MSX) is considered a treatment option in patients with metastatic renal cell carcinoma (mRCC) at diagnosis, but its role in the targeted therapy era is unclear. We sought to describe the utilization trends of MSX and survival outcomes in a large US cohort.

New therapies for castrate-resistant prostate cancer

INTRODUCTION: Prostate cancer is the second leading cause of cancer death in men in the USA, and most of these deaths will occur as a result of castrate-resistant prostate cancer (CRPC) that has progressed despite androgen deprivation therapy. There has been better understanding of castration resistance and molecular mechanisms of prostate cancer progression recently, leading to new treatment strategies. AREAS COVERED: This review focuses on emerging and new therapies for castrate-resistant prostate cancer, including hormonal therapy, immunotherapy and cytotoxic agents. EXPERT OPINION: New treatment strategies have been developed in recent years and, with improved understanding of advanced CRPC, additional targeted treatments are expected in the near future. Further cost effectiveness research of these treatments is warranted before dissemination of these promising agents.     

The Effect of Weight Change During Treatment With Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma

BackgroundThe relationship between weight change during treatment and survival remains poorly characterized in patients with metastatic renal cell carcinoma (mRCC).Patients and MethodsIn this retrospective analysis we included 3311 patients with mRCC treated in phase II/III first-line or second-line targeted therapy clinical trials and assessed the effect of weight change on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) at 6 and 12 weeks from treatment initiation. Weight change was defined as weight loss (≥5% reduction), weight gain (≥2% increase), or stable weight from baseline. Survival analyses were performed using the Kaplan–Meier method and adjusted for known prognostic factors using Cox regression multivariable analysis.ResultsOverall, 1916 (58%) had stable weight, 936 (28%) had weight loss, and 459 (14%) had weight gain at 12 weeks. Patients with weight loss at 12 weeks had inferior OS compared with those with stable weight (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.322-1.688; P < .0001; median OS 18.7 vs. 26.9 months), and shorter PFS (HR, 1.315; 95% CI, 1.189-1.455; P < .0001; median PFS, 7.2 vs. 10.1 months). The ORRs for patients with weight loss, stable weight, and weight gain at 12 weeks were 23.4% (n = 219/936), 32.1% (n = 615/1916), and 35.9% (n = 165/459), respectively (adjusted odds ratio, 0.715; P = .03). Findings were consistent at 6 weeks. Adverse events were similar between groups.ConclusionWe showed that mRCC patients who experience weight loss during treatment have worse outcomes compared with patients with stable weight at 6 and 12 weeks of treatment. Weight loss at 6 weeks from treatment initiation might be an early clinical biomarker of worse survival and might provide prognostic utility.     

Comparative Effectiveness of Radical Prostatectomy Versus External Beam Radiation Therapy Plus Brachytherapy in Patients with High-risk Localized Prostate Cancer

A previous study comparing external beam radiation therapy with/without brachytherapy (EBRT ± BT) and radical prostatectomy (RP) for high-risk localized prostate cancer (PCa) did not find a difference in overall survival (OS) between the treatments. However, this study was limited by short follow-up and assessment of OS in patients of divergent age and comorbidities. We therefore compared OS of EBRT + BT versus RP in comparatively young (≤65 yr) and healthy men (Charlson Comorbidity Index = 0) with high-risk localized PCa in the National Cancer Database. Inverse probability of treatment weighting (IPTW) adjustment was used to balance baseline characteristics. Median follow-up was 92 mo (interquartile range 78–108). Using IPTW-adjusted Cox regression analysis, EBRT + BT was associated with a higher risk of all-cause mortality compared with RP (hazard ratio = 1.22, 95% confidence interval 1.05–1.43). In young and healthy men presenting with high-risk localized PCa, RP showed statistically significant OS benefit compared with EBRT + BT.

The impact of kidney function on the outcome of metastatic renal cell carcinoma patients treated with vascular endothelial growth factor-targeted therapy

BACKGROUND:

A study was undertaken to investigate the effect of baseline renal function on treatment outcome in patients treated with vascular endothelial growth factor (VEGF)‐targeted therapy for metastatic renal cell carcinoma (mRCC).

METHODS:

Retrospective data from 6 North American cancer centers (3 US and 3 Canadian) were pooled to identify patients with mRCC treated with VEGF‐targeted therapy. Patient characteristics, response rate, time to treatment failure, and overall survival were collected. The Modification of Diet in Renal Disease formula was used at therapy initiation for calculation of glomerular filtration rate (GFR).

RESULTS:

Five hundred twenty‐nine patients with mRCC who received sunitinib (n = 323), sorafenib (n = 165), or bevacizumab (n = 41) were included in this analysis. Patient characteristics included: 74% male, median age 61 years, and median GFR 60.1 mL/min/1.73 m² (range, 6.5‐174.2). On univariate analysis, patients with a GFR <60 (n = 262) were more likely to have had a previous nephrectomy (P < .0001) and to be older (P < .0001), but were less likely to have poor prognostic features such as anemia (P = .041), hypercalcemia (P = .008), neutrophilia (P = .039), thrombocytosis (P < .0001), short diagnosis to treatment interval (P = .007), and low Karnofsky performance status (P = .051). GFR <60, when adjusted for poor risk factors, did not have an impact on type of objective response (odds ratio, 1.31; 95% confidence interval [CI], 0.74‐2.32; P = .359), time to treatment failure (hazard ratio [HR], 0.97; 95% CI, 0.79‐1.19; P = .772), or overall survival (HR, 0.90; 95% CI, 0.69‐1.17; P = .439).

CONCLUSIONS:

Renal function at therapy initiation does not adversely affect the efficacy of VEGF‐targeted therapy in mRCC. Clinicians should not avoid treating patients with impaired baseline renal function. Cancer 2011;. © 2011 American Cancer Society.