A B S T R A C T PurposeTivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), -2, and -3. This phase III trial compared tivozanib with sorafenib as initial targeted therapy in patients with metastatic renal cell carcinoma (RCC). Patients and MethodsPatients with metastatic RCC, with a clear cell component, prior nephrectomy, measurable disease, and 0 or 1 prior therapies for metastatic RCC were randomly assigned to tivozanib or sorafenib. Prior VEGF-targeted therapy and mammalian target of rapamycin inhibitor were not permitted. The primary end point was progression-free survival (PFS) by independent review. ResultsA total of 517 patients were randomly assigned to tivozanib (n ϭ 260) or sorafenib (n ϭ 257). PFS was longer with tivozanib than with sorafenib in the overall population (median, 11.9 v 9.1 months; hazard ratio [HR], 0.797; 95% CI, 0.639 to 0.993; P ϭ .042). One hundred fifty-six patients (61%) who progressed on sorafenib crossed over to receive tivozanib. The final overall survival (OS) analysis showed a trend toward longer survival on the sorafenib arm than on the tivozanib arm (median, 29.3 v 28.8 months; HR, 1.245; 95% CI, 0.954 to 1.624; P ϭ .105). Adverse events (AEs) more common with tivozanib than with sorafenib were hypertension (44% v 34%) and dysphonia (21% v 5%). AEs more common with sorafenib than with tivozanib were hand-foot skin reaction (54% v 14%) and diarrhea (33% v 23%). ConclusionTivozanib demonstrated improved PFS, but not OS, and a differentiated safety profile, compared with sorafenib, as initial targeted therapy for metastatic RCC.

Background-In the ongoing phase 3, CheckMate 214 trial, nivolumab plus ipilimumab improved overall survival compared with sunitinib in patients with intermediate or poor risk, previously untreated, advanced renal cell carcinoma. We aimed to assess whether health-related quality of life (HRQoL) could be used to further describe the benefit-risk profile of nivolumab plus ipilimumab versus sunitinib. Methods-In the phase 3, randomised, controlled, CheckMate 214 trial, patients aged 18 years and older with previously untreated, advanced or metastatic renal cell carcinoma with a clear-cell component were recruited from 175 hospitals and cancer centres in 28 countries. Patients were categorised by risk status into favourable, intermediate, and poor risk subgroups and randomly assigned (1:1) to open-label nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four

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Background In the phase 3, double-blind, placebo-controlled PROSPER trial of patients with non-metastatic castration-resistant prostate cancer, enzalutamide significantly improved metastasis-free survival (primary endpoint). Here, we report the results of patient-reported outcome (PRO) measures of this study. Methods Patients ≥18 years of age with non-metastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of ≤10 months were randomised (2:1) via interactive voice/web recognition system to receive enzalutamide (160 mg/day) or placebo. Randomisation was stratified by prostate-specific-antigen-doubling time (<6 months vs ≥6 months) and baseline use of a bone-targeting agent (yes or no). The primary endpoint was metastasis-free survival (MFS), reported elsewhere. Exploratory endpoints, reported here, included pain progression and health-related quality of life (HRQoL), assessed by the Brief Pain Inventory Short Form (BPI-SF), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-PR25), the Functional Assessment of Cancer Therapy-Prostate (FACT-P), and the EuroQoL 5-Dimensions 5-Levels health questionnaire visual analogue scale (EQ-VAS). Patients completed questionnaires at baseline, Week 17, and every 16 weeks thereafter during treatment. Pre-defined questionnaire thresholds were used to identify clinically meaningful changes. Enrollment for PROSPER is complete and follow-up continues. This trial is registered with ClinicalTrials.gov (NCT02003924). Findings Patients were enrolled from 26 November 2013 to 28 June 2017. Median followup time for all patients was 18•5 months (interquartile range [IQR] 10•7-29•2 months) in the enzalutamide group and 15•1 months (IQR 7•4-25•9 months) in the placebo group. Patients randomised to receive enzalutamide or placebo had similar baseline PRO scores. Changes in 6 Further analyses are needed to determine potential associations between pain, HRQoL, and disease progression in non-metastatic castration-resistant prostate cancer. Implications of all the available evidence As patients with non-metastatic castration-resistant prostate cancer generally have low levels of pre-treatment pain and favourable HRQoL compared to patients with advanced disease, treatments should aim to improve clinical outcomes while maintaining pain control and HRQoL. The demonstrated efficacy, tolerability, and HRQoL profile suggest that enzalutamide represents a treatment option for patients with non-metastatic castrationresistant prostate cancer. PROSPER patient recruitment sites, principal investigators and patients recruited by site* Country Site # Study centre Principal investigator # patients randomised Denmark 421 Herlev Hospital Per Rathenborg