PURPOSE Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS ARCHES (ClinicalTrials.gov identifier: NCT02677896 ) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival. RESULTS As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT ( P < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events. CONCLUSION Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer.
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In primary analysis, enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC); however, overall survival data were immature. In the phase III, double-blind, global ARCHES trial (ClinicalTrials.gov identifier: NCT02677896 ), 1,150 patients with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg once daily) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use. Here, we report the final prespecified analysis of overall survival (key secondary end point) and an update on rPFS, other secondary end points, and safety. After unblinding, 180 (31.3%) progression-free patients randomly assigned to placebo plus ADT crossed over to open-label enzalutamide plus ADT. As of May 28, 2021 (median follow-up, 44.6 months), 154 of 574 patients randomly assigned to enzalutamide plus ADT and 202 of 576 patients randomly assigned to placebo plus ADT had died. Enzalutamide plus ADT reduced risk of death by 34% versus placebo plus ADT (median not reached in either group; hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P < .001). Enzalutamide plus ADT continued to improve rPFS and other secondary end points. Adverse events were generally consistent with previous reports of long-term enzalutamide use. In conclusion, enzalutamide plus ADT significantly prolongs survival versus placebo plus ADT in patients with mHSPC.
Objectives: To assess epidemiological and chronological trends of upper urinary tract stones in Japan in 2015.Methods: Patients with a first episode of upper urinary tract stones in 2015 were enrolled in this nationwide survey. The study included all hospitals approved by the Japanese Board of Urology, therefore covering most of the hospitals where urologists practice in Japan. The annual incidence and composition of urolithiasis were evaluated by age and sex. These results were compared with the previous results of the nationwide surveys from 1965 to 2005 to analyze temporal trends. Results: The estimated annual incidence of a first-episode upper urinary tract stone in 2015 was 137.9 (191.9 in men and 86.9 in women) per 100 000. The estimated agestandardized first-episode upper urinary tract stone incidence in 2015 was 107.8 (150.6 in men and 63.3 in women) per 100 000, which did not represent a significant increase since 2005. An equivalent incidence was observed in patients aged >50 years, whereas a reduced incidence was observed in patients aged <50 years in both sexes. The proportion of patients who received percutaneous nephrolithotomy and/or ureteroscopy increased by approximately fivefold in the past 10 years. Conclusions: The steady increase in the annual incidence of upper urinary tract stones since 1955 leveled off in 2015. The current results show novel trends in the incidence and treatment modalities in the nationwide surveys of urolithiasis in Japan.
AimsMany investigators have speculated that hyperintense plaques (HIPs) of the carotid artery on non-contrast T1-weighted imaging (T1WI) in magnetic resonance indicate the presence of mural or intraplaque haemorrhage containing methemoglobin. Coronary plaque imaging with T1WI is challenging, and the clinical significance of coronary HIP on T1WI remains unknown. The aim of this study was to compare HIPs on T1WI with coronary plaque morphology assessed by optical coherence tomography (OCT), which allows us to identify not only plaque rupture, but also fibrous cap thickness and intracoronary thrombus in vivo, in patients with angina pectoris.Methods and resultsTwenty-six lesions from 26 patients with either stable or unstable angina pectoris were examined in this study. All patients underwent T1WI within 24 h before the day on which invasive coronary angiography was performed, and pre-interventional OCT was performed on a native atherosclerotic lesion, considered to be the culprit lesion. Of the 26 lesions studied, 16 (62%) were HIPs and 10 (38%) were non-HIPs. The signal intensity of the coronary plaque to cardiac muscle ratio in HIPs was significantly higher than that in non-HIPs. There were no significant differences in the frequency of lipid-rich plaque, thin-cap fibroatheroma, plaque rupture, and calcification between HIPs and non-HIPs. In contrast, the frequency of thrombus was significantly higher in HIPs than in non-HIPs (P = 0.004).ConclusionThis study shows that the HIPs on T1WI in angina patients relate to the presence of intracoronary thrombus as detected by OCT imaging.
Background: Myocardial fractional flow reserve (FFR) is useful in the evaluation of coronary lesion ischemia. However, the impact of lesion length on FFR has not been adequately assessed. Hypothesis: We hypothesized that lesion length would influence functional significance in intermediate coronary lesions. Methods: FFR measurements were assessed in 136 patients (163 lesions) with stable angina who had >40% stenotic coronary lesion by quantitative coronary angiography (QCA). One hundred sixty-three lesions were classified as intermediate (40%-70% stenosis; n=107; group I) or significant (≥70%; n=56; group S) by QCA. We assessed the relationships between lesion length, coronary stenosis, and FFR in these 163 lesions. Results: Regression analysis revealed an inverse correlation between the percentage of diameter stenosis (%DS) and FFR in group S (r = −0.83, P < 0.0001). In group I, no significant correlation was found between %DS and FFR (r = −0.06, P = 0.55), whereas lesion length was significantly inversely correlated with FFR (r = −0.79, P < 0.0001). Receiver operating characteristic curve analysis demonstrated that the best cutoff value for predicting an FFR value <0.80 was a lesion length >16.1 mm in group I (sensitivity, 86%; specificity, 94%). Conclusions: These study findings suggest that lesion length has a physiologically significant impact on intermediate-grade coronary lesions.
limited treatment options after failure of novel hormonal therapy (NHT). We report efficacy and safety results of expanded cohort 6 in mCRPC.Methods: Eligible pts had measurable disease, radiographic progression in soft tissue after enzalutamide and/or abiraterone, and ECOG PS of 0 or 1. Prior chemotherapy for metastatic castration-sensitive prostate cancer (mCSPC) was permitted. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. CT/MRI scans were performed Q6W for 52W and Q12W thereafter. The primary endpoint was ORR by investigator (INV) per RECIST 1.1. Other endpoints included safety, PFS, and OS.
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