Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone.

Background: Abiraterone and cabazitaxel improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted an open-label phase I/II trial of cabazitaxel plus abiraterone to assess the antitumor activity and tolerability in patients with progressive mCRPC after docetaxel (phase I), and after docetaxel and abiraterone (phase II) (NCT01511536).

Patients And Methods: The primary objectives were to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus abiraterone (phase I), and the prostate-specific antigen (PSA) response defined as a ≥ 50% decrease confirmed ≥3 weeks later with this combination (phase II).

Hypertension and Angiotensin System Inhibitors in Patients with Metastatic Renal Cell Carcinoma.

Arterial hypertension (HTN) is a class effect of anti-vascular endothelial growth factor (VEGF) therapies, including the monoclonal antibody bevacizumab. Data are conflicting regarding the role of the renin-angiotensin system on angiogenesis and recent data suggest that the use of angiotensin system inhibitors (ASIs; angiotensin receptor blockers or angiotensin-converting enzyme inhibitors) is associated with improved survival in metastatic renal cell carcinoma (mRCC), particularly when used with VEGF targeted therapies. The aim of this review is to discuss the available treatment options for mRCC and associated incidence of hypertension as well as summarize the known data about ASIs use and mRCC.

Updated European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma.

Unlabelled: The European Association of Urology Renal Cell Carcinoma (RCC) guidelines panel updated their recommendation on adjuvant therapy in unfavourable, clinically nonmetastatic RCC following the recently reported results of a second randomised controlled phase 3 trial comparing 1-yr sunitinib to placebo for high-risk RCC after nephrectomy (S-TRAC). On the basis of conflicting results from the two available studies, the panel rated the quality of the evidence, the harm-to-benefit ratio, patient preferences, and costs. Finally, the panel, including representatives from a patient advocate group (International Kidney Cancer Coalition) voted and reached a consensus to not recommend adjuvant therapy with sunitinib for patients with high-risk RCC after nephrectomy.

A Systematic Review and Meta-analysis Comparing the Effectiveness and Adverse Effects of Different Systemic Treatments for Non-clear Cell Renal Cell Carcinoma.

Context: While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown.

Objective: To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC.

Evidence Acquisition: Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016.

Burned-Out Testis Tumors in Asymptomatic Infertile Men: Multiparametric Sonography and MRI Findings.

Multiparametric testicular ultrasound and magnetic resonance imaging (MRI) findings were analyzed in a series of 10 infertile asymptomatic men presenting with pathologically confirmed burned-out testicular tumors. Color/power Doppler ultrasound (CDUS), shear wave elastography (SWE), contrast-enhanced ultrasonography (CEUS), and MRI were performed on 10, 5, 6, and 7 patients, respectively. All lesions appeared as a hypoechoic and hypovascular nodular area at CDUS, SWE, CEUS CDUS, and CEUS (if performed).

[CCAFU french national guidelines 2016-2018 on renal cancer].

The previous guidelines from the Cancer Committee of the Association Française d'Urologie were published in 2013. We wanted this new version to be simple, clear and straightforward. All significant recent publications on kidney cancer have been included.

Cabozantinib for the treatment of renal cell carcinoma.

Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy. Areas covered:The preclinical development and scientific rationale, pharmacokinetics, and clinical efficacy and safety of cabozantinib for the treatment of advanced RCC are reviewed.

Predicting and preventing thromboembolic events in patients receiving cisplatin-based chemotherapy for germ cell tumours.

Background: Patients with germ cell tumours (GCT) receiving cisplatin-based chemotherapy are at high risk of thromboembolic events (TEE). Previously, we identified serum lactate dehydrogenase (LDH) and body surface area (BSA) as independent predictive factors for TEE. The aim of this study was to validate these predictive factors and to assess the impact of thromboembolism prophylaxis in patients at risk of deep venous thrombosis (DVT).

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma.

Purpose: Nivolumab, an anti-PD-1 immune checkpoint inhibitor, improved overall survival versus everolimus in a phase 3 trial of previously treated patients with metastatic renal cell carcinoma (mRCC). We investigated immunomodulatory activity of nivolumab in a hypothesis-generating prospective mRCC trial.

Experimental Design: Nivolumab was administered intravenously every 3 weeks at 0.

Localized chromophobe carcinomas treated by nephron-sparing surgery have excellent oncologic outcomes.

Objective: To evaluate the oncologic outcomes of nephron-sparing surgery (NSS) for localized chromophobe renal cell carcinoma (cRCC).

Material And Methods: We performed a multicenter international study involving the French Network for Research on Kidney Cancer (UroCCR) and 5 international teams. Data from 808 patients treated with NSS between 2004 and 2014 for non-clear cell RCCs were analyzed.

Open-label phase 2 trial of first-line everolimus monotherapy in patients with papillary metastatic renal cell carcinoma: RAPTOR final analysis.

Background: Papillary histology accounts for 10-15% of renal cell carcinoma (RCC), and treatment options for patients with this subtype are limited. The RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe; ClinicalTrials.gov, NCT00688753) study evaluated first-line everolimus in patients with papillary metastatic RCC (mRCC).

Chemotherapy in hormone-sensitive metastatic prostate cancer: Evidences and uncertainties from the literature.

Data from the literature support with strong evidence the addition of docetaxel to androgen-deprivation therapy (ADT) for men with metastatic prostate cancer, and starting therapy for the first time. A meta-analysis of three randomized controlled trials showed a significant improvement of overall survival when ADT was combined with docetaxel when compared to ADT alone (HR=0.77; 95% CI: 0.

Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations.

Purpose: Obesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC.

Methods: The impact of BMI (high BMI: ≥ 25 kg/m v low BMI: < 25 kg/m) on overall survival (OS) and treatment outcome with targeted therapy was investigated in 1,975 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and in an external validation cohort of 4,657 patients.

Insurance status and disparities in disease presentation, treatment, and outcomes for men with germ cell tumors.

Background: People aged 26 to 34 years represent the greatest proportion of the uninsured, and they have the highest incidence of testicular cancers. The aim of this study was to investigate the association between insurance status and cancer outcomes in men diagnosed with germ cell tumors.

Methods: The Surveillance, Epidemiology, and End Results database was used to identify 10,211 men diagnosed with germ cell gonadal neoplasms from 2007 to 2011.

Partial nephrectomy versus ablative therapy for the treatment of renal tumors in an imperative setting.

Purpose: To compare partial nephrectomy (PN) and percutaneous ablative therapy (AT) for renal tumor in imperative indication of nephron-sparing technique (NST).

Materials And Methods: Between 2000 and 2015, 284 consecutive patients with a kidney tumor in an imperative indication of NST were retrospectively included in a multicenter study. PN [open (n = 146), laparoscopic (n = 9), or robotic approach (n = 17)] and AT [radiofrequency ablation (n = 104) or cryoablation (n = 8)] were performed for solitary kidney (n = 146), bilateral tumor (n = 78), or chronic kidney disease (CKD) (n = 60).

Whole-Exome Sequencing in Two Extreme Phenotypes of Response to VEGF-Targeted Therapies in Patients With Metastatic Clear Cell Renal Cell Carcinoma.

Advances in next-generation sequencing have provided a unique opportunity to understand the biology of disease and mechanisms of sensitivity or resistance to specific agents. Renal cell carcinoma (RCC) is a heterogeneous disease and highly variable clinical responses have been observed with vascular endothelial growth factor (VEGF)-targeted therapy (VEGF-TT). We hypothesized that whole-exome sequencing analysis might identify genotypes associated with extreme response or resistance to VEGF-TT in metastatic (mRCC).

Early PSA response is an independent prognostic factor in patients with metastatic castration-resistant prostate cancer treated with next-generation androgen pathway inhibitors.

Background: The optimal use of new therapies in metastatic castration-resistant prostate cancer (mCRPC) remains to be clarified. Prostate-specific antigen (PSA) response used as a pharmacodynamic end-point may help identify patients with early resistance to new androgen receptor-pathway inhibitors. We aimed to determine the clinical significance of early PSA response (EPR) during therapy with enzalutamide, abiraterone acetate (AA) and orteronel in mCRPC.

Safety of available treatment options for renal cell carcinoma.

Introduction: For many years, cytokines (high-dose interleukin (IL)-2 and interferon (IFN)) have been the unique available treatment options for metastatic renal cell carcinoma (mRCC) and they provided durable but modest responses at the cost of significant toxicities. To date, targeted therapies have replaced cytokine therapy due to higher response rates and more favorable toxicity profiles. The major classes of targeted therapy for mRCC include tyrosine kinase inhibitors, monoclonal antibody against vascular endothelial grow factors and inhibitors of the mammalian target of rapamycin.

Mutations in TSC1, TSC2, and MTOR Are Associated with Response to Rapalogs in Patients with Metastatic Renal Cell Carcinoma.

Purpose: We examined the hypothesis that mutations in mTOR pathway genes are associated with response to rapalogs in metastatic renal cell carcinoma (mRCC).

Experimental Design: We studied a cohort of mRCC patients who were treated with mTOR inhibitors with distinct clinical outcomes. Tumor DNA from 79 subjects was successfully analyzed for mutations using targeted next-generation sequencing of 560 cancer genes.

Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data.

Background: Results from large randomised controlled trials combining docetaxel or bisphosphonates with standard of care in hormone-sensitive prostate cancer have emerged. In order to investigate the effects of these therapies and to respond to emerging evidence, we aimed to systematically review all relevant trials using a framework for adaptive meta-analysis.

Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, LILACS, and the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant randomised controlled trials (published, unpublished, and ongoing) comparing either standard of care with or without docetaxel or standard of care with or without bisphosphonates for men with high-risk localised or metastatic hormone-sensitive prostate cancer.

Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

Background: Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene.

Objective: To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression.

Design, Setting, And Participants: A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene.

Statins and survival outcomes in patients with metastatic renal cell carcinoma.

Background: A growing body of evidence has demonstrated the anti-neoplastic activity of statins. The objective of this study was to investigate the effect of statin use on survival in patients with metastatic renal cell carcinoma (mRCC) treated in the modern therapy era.

Patients And Methods: We conducted a pooled analysis of mRCC patients treated on phase II and III clinical trials.

Vinflunine-gemcitabine versus vinflunine-carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1).

Background: There is no standard first-line chemotherapy for advanced urothelial carcinoma (aUC) in cisplatin-ineligible (cisplatin-unfit) patients. The study assessed the efficacy and tolerability profile of two vinflunine-based cytotoxic regimens in this setting.

Patients And Methods: Patients with aUC a creatinine clearance (CrCl) of <60 but ≥30 ml/min, performance status 0 or 1 and no prior chemotherapy for advanced disease were randomized (1 : 1).

Everolimus Versus Sunitinib Prospective Evaluation in Metastatic Non-Clear Cell Renal Cell Carcinoma (ESPN): A Randomized Multicenter Phase 2 Trial.

Background: Sunitinib and everolimus are standard first-line and second-line therapies, respectively, in clear cell renal cell carcinoma (ccRCC).

Objective: To conduct a randomized phase 2 trial comparing sunitinib and everolimus in non-clear cell RCC (non-ccRCC).

Design, Setting, And Participants: Patients with metastatic, non-ccRCC, or ccRCC with >20% sarcomatoid features (ccSRCC) were randomized to receive sunitinib or everolimus with crossover at disease progression.