Showing papers in "The New England Journal of Medicine in 2019"
University of Glasgow1, Brigham and Women's Hospital2, Yale University3, University of Copenhagen4, University of Missouri–Kansas City5, National University of Cordoba6, Wrocław Medical University7, Harvard University8, University of Minnesota9, Charles University in Prague10, Saarland University11, Taipei Veterans General Hospital12, National Yang-Ming University13, Slovak Medical University14, Fudan University15, Libin Cardiovascular Institute of Alberta16, University of Calgary17, Sofia Medical University18, University of Gothenburg19, Semmelweis University20, University of São Paulo21, Montreal Heart Institute22, University of Toronto23, Uppsala University24, University of Wisconsin-Madison25, AstraZeneca26
TL;DR: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than amongThose who received placebo, regardless of the presence or absence of diabetes.
Abstract: Background In patients with type 2 diabetes, inhibitors of sodium–glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-ind...
3,541 citations
TL;DR: The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium–glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined.
Abstract: Background The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium–glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. Methods We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. Results We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, ...
3,430 citations
Royal North Shore Hospital1, The George Institute for Global Health2, Concord Repatriation General Hospital3, University of Sydney4, Imperial College London5, Harvard University6, New York University7, Janssen Pharmaceutica8, Indiana University – Purdue University Indianapolis9, Veterans Health Administration10, University of Chicago11, Kolling Institute of Medical Research12, Utah System of Higher Education13, University of British Columbia14, University College London15, Peking University16, Lunenfeld-Tanenbaum Research Institute17, Stanford University18
TL;DR: In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years.
Abstract: Background Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium...
3,233 citations
Scott & White Hospital1, Columbia University2, Georgetown University3, Rutgers University4, Cleveland Clinic5, Laval University6, University of British Columbia7, New York University8, University of Washington9, Emory University10, Lankenau Institute for Medical Research11, University of Pennsylvania12, Morristown Medical Center13, University of London14
TL;DR: Among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery.
Abstract: Background Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) an...
2,917 citations
Harvard University1, University of Michigan2, PinnacleHealth System3, St. Luke's Hospital4, Spectrum Health5, Mount Sinai Hospital6, Scripps Research Institute7, University of Kansas8, Yale University9, Johns Hopkins University10, Alfred Hospital11, McGill University12, Saint Francis University13, University of Pittsburgh14, Mayo Clinic15, Medtronic plc16, Paradigm17
TL;DR: In patients with severe aortic stenosis who were at low surgical risk, TAVR with a self‐expanding supraannular bioprosthesis was noninferior to surgery with respect to the composite end point of death or disabling stroke at 24 months.
Abstract: Background Transcatheter aortic-valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis who are at increased risk for death from surgery; less is know...
2,240 citations
University of Pennsylvania1, University of Chicago2, University of Melbourne3, Emory University4, University of Cologne5, University of Kansas6, Medical University of Vienna7, Ohio State University8, University of California, San Francisco9, University of Texas MD Anderson Cancer Center10, Université de Montréal11, University of Minnesota12, McMaster University13, Royal Prince Alfred Hospital14, University of Würzburg15, Karolinska Institutet16, University of Michigan17, University of Oslo18, Novartis19, University of Lyon20
TL;DR: The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
Abstract: Background Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. Methods We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. Results A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 ...
2,086 citations
TL;DR: Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivoliumab alone than in those who received ipil optimumab alone, with no apparent loss of quality of life in the patients whoreceived regimens containing nivolinumab.
Abstract: BACKGROUND
Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.
METHODS
We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group.
RESULTS
At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted.
CONCLUSIONS
Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).
2,086 citations
Cleveland Clinic1, Fox Chase Cancer Center2, Ivano-Frankivsk National Medical University3, Queen Mary University of London4, Laval University5, University of Colorado Colorado Springs6, University College Dublin7, University of Tübingen8, Taipei Veterans General Hospital9, Osaka City University10, Merck & Co.11, Georgetown University12
TL;DR: Treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression‐free survival, as well as a higher objective response rate, than treatment with sunitin ib among patients with previously untreated advanced renal‐cell carcinoma.
Abstract: Background The combination of pembrolizumab and axitinib showed antitumor activity in a phase 1b trial involving patients with previously untreated advanced renal-cell carcinoma. Whether pembrolizumab plus axitinib would result in better outcomes than sunitinib in such patients was unclear. Methods In an open-label, phase 3 trial, we randomly assigned 861 patients with previously untreated advanced clear-cell renal-cell carcinoma to receive pembrolizumab (200 mg) intravenously once every 3 weeks plus axitinib (5 mg) orally twice daily (432 patients) or sunitinib (50 mg) orally once daily for the first 4 weeks of each 6-week cycle (429 patients). The primary end points were overall survival and progression-free survival in the intention-to-treat population. The key secondary end point was the objective response rate. All reported results are from the protocol-specified first interim analysis. Results After a median follow-up of 12.8 months, the estimated percentage of patients who were alive at 12 months was 89.9% in the pembrolizumab-axitinib group and 78.3% in the sunitinib group (hazard ratio for death, 0.53; 95% confidence interval [CI], 0.38 to 0.74; P Conclusions Among patients with previously untreated advanced renal-cell carcinoma, treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression-free survival, as well as a higher objective response rate, than treatment with sunitinib. (Funded by Merck Sharp & Dohme; KEYNOTE-426 ClinicalTrials.gov number, NCT02853331.).
2,075 citations
TL;DR: Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than amongThose who received placebo.
Abstract: Background Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events. Methods We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Results A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P Conclusions Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361 .).
1,915 citations
Memorial Sloan Kettering Cancer Center1, Netherlands Cancer Institute2, Cleveland Clinic3, Institut Gustave Roussy4, University of Texas MD Anderson Cancer Center5, University of Glasgow6, University of British Columbia7, University of Lyon8, Osaka University9, University of Ulsan10, Russian Railways11, McGill University12, Medical University of Vienna13, The Royal Marsden NHS Foundation Trust14, Georgetown University15, University of Tübingen16, Pfizer17, Harvard University18
TL;DR: Progression‐free survival was significantly longer with avelumab plus axitinib than with sunit inib among patients who received these agents as first‐line treatment for advanced renal‐cell carcinoma.
Abstract: Background In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously...
1,597 citations
Memorial Sloan Kettering Cancer Center1, Complutense University of Madrid2, Samsung Medical Center3, Hospital Italiano de Buenos Aires4, Aix-Marseille University5, University Hospital of Lausanne6, National and Kapodistrian University of Athens7, Bristol-Myers Squibb8, Emory University9, Princess Alexandra Hospital10, AstraZeneca11
TL;DR: First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level.
Abstract: Background In an early-phase study involving patients with advanced non–small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab mono...
TL;DR: Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo.
Abstract: Background Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medi...
TL;DR: This research presents a meta-modelling architecture that automates the very labor-intensive and therefore time-heavy and expensive and therefore expensive and expensive process of manually cataloging and cataloging patient-provider interactions.
Abstract: Machine Learning in Medicine In this view of the future of medicine, patient–provider interactions are informed and supported by massive amounts of data from interactions with similar patients. The...
TL;DR: Among patients with HER2‐positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T‐DM1 than with trastuzumab alone.
Abstract: Background Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)–targeted therapy have a worse pro...
TL;DR: Treatment with alpelisib–fulvestrant prolonged progression‐free survival among patients with PIK3CA‐mutated, HR‐positive, HER2‐negative advanced breast cancer who had received endocrine therapy previously.
Abstract: Background PIK3CA mutations occur in approximately 40% of patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer. The PI3Kα-sp...
Tel Aviv University1, Katholieke Universiteit Leuven2, Fox Chase Cancer Center3, Sungkyunkwan University4, University College London5, Ruhr University Bochum6, Agostino Gemelli University Polyclinic7, Integra Telecom8, Technische Universität München9, Memorial Sloan Kettering Cancer Center10, AstraZeneca11, Merck & Co.12, University of Chicago13
TL;DR: Among patients with a germline BRCA mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo, and there was no significant between-group difference in health-related quality of life.
Abstract: Background Patients with a germline BRCA1 or BRCA2 mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate–ribose) polymerase (PARP) in...
Harvard University1, University of Glasgow2, University of Minnesota3, Fudan University4, National University of Cordoba5, Baylor University Medical Center6, University Medical Center Groningen7, Université de Montréal8, Medical University of South Carolina9, University of Lorraine10, University of Barcelona11, Northwestern University12, Charité13, University of Groningen14, Cardiovascular Institute of the South15, University of São Paulo16, Semmelweis University17, Novartis18
TL;DR: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failureand an ejection fraction of 45% or higher, and among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit in patients with lower ejection fractions and in women.
Abstract: Background The angiotensin receptor–neprilysin inhibitor sacubitril–valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients ...
TL;DR: In patients with progressive fibrosing interstitial lung diseases, the annual rate of decline in the FVC was significantly lower among patients who received nintedanib than among those who received placebo.
Abstract: Background Preclinical data have suggested that nintedanib, an intracellular inhibitor of tyrosine kinases, inhibits processes involved in the progression of lung fibrosis. Although the ef...
TL;DR: A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival, and both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD.
Abstract: Background Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the ...
Hospital Universitario La Paz1, Memorial Sloan Kettering Cancer Center2, Gynecologic Oncology Group3, Medical University of South Carolina4, Rigshospitalet5, McGill University Health Centre6, Ohio State University7, Thomas Jefferson University8, Medical College of Wisconsin9, Technion – Israel Institute of Technology10, GlaxoSmithKline11, University of Arizona12, University of Girona13, University of Pennsylvania14, Vita-Salute San Raffaele University15
TL;DR: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival thanThose who received placebo, regardless of the presence or absence of homologous-recombination deficiency.
Abstract: Background Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients ...
TL;DR: Elexacaftor-tezacaft or-ivacaft or was efficacious in patients with cystic fibrosis with Phe508del-minimal function genotypes, in whom previous CFTR modulator regimens were ineffective.
Abstract: Background Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, and nearly 90% of patients have at least one ...
TL;DR: Comparing vitamin D with placebo did not result in a lower incidence of invasive cancer or cardiovascular events than placebo, and Supplementation with vitamin D was not associated with a lower risk of either of the primary end points.
Abstract: Background It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease, and data from randomized trials are limited. Methods We conducted a nationwide, randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (cholecalciferol) at a dose of 2000 IU per day and marine n−3 (also called omega-3) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes). Secondary end points included site-specific cancers, death from cancer, and additional cardiovascular events. This article reports the results of the comparison of vitamin D with placebo. Results A total of 25,871 participants, including 5106 black participants, underwent randomization....
TL;DR: The initial toxicity profile of a BCMA‐directed cellular immunotherapy for patients with relapsed or refractory multiple myeloma is reported andCAR T‐cell expansion was associated with responses, and CAR T cells persisted up to 1 year after the infusion.
Abstract: Background Preclinical studies suggest that bb2121, a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA), has potential for the treatment of multi...
TL;DR: E‐cigarettes were more effective for smoking cessation than nicotine‐replacement therapy, when both products were accompanied by behavioral support.
Abstract: Background E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-...
TL;DR: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation.
Abstract: Background Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining mainte...
TL;DR: This siteless study design provides a foundation for large-scale pragmatic studies in which outcomes or adherence can be reliably assessed with user-owned devices and the probability of receiving an irregular pulse notification was low.
Abstract: Background Optical sensors on wearable devices can detect irregular pulses. The ability of a smartwatch application (app) to identify atrial fibrillation during typical use is unknown. Met...
Shanghai Jiao Tong University1, University of Ottawa2, AmeriCorps VISTA3, Nagasaki University4, Seoul National University5, National Taiwan University6, Yale University7, Czech University of Life Sciences Prague8, University of Tartu9, Huazhong University of Science and Technology10, University of Washington11, Health Effects Institute12
TL;DR: The data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe, and reinforce the evidence of a link between mortality and PM concentration established in regional and local studies.
Abstract: BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias.METHODS: We evaluated the assoc ...
TL;DR: The analysis indicates that the prevalence of adult obesity and severe obesity will continue to increase nationwide, with large disparities across states and demographic subgroups.
Abstract: Background Although the national obesity epidemic has been well documented, less is known about obesity at the U.S. state level. Current estimates are based on body measures reported by pe...
TL;DR: The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintinganib than with placebo.
Abstract: Background Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. Methods We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. Results A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was -52.4 ml per year in the nintedanib group and -93.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P = 0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of -0.21 (95% CI, -0.94 to 0.53; P = 0.58) and 1.69 (95% CI, -0.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. Conclusions Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo. (Funded by Boehringer Ingelheim; SENSCIS ClinicalTrials.gov number, NCT02597933.).
University of Sydney1, Guy's and St Thomas' NHS Foundation Trust2, University of British Columbia3, Harvard University4, Monash University5, Royal Prince Alfred Hospital6, Garvan Institute of Medical Research7, St. Vincent's Health System8, Auckland City Hospital9, Sydney Adventist Hospital10, Mater Misericordiae University Hospital11, University College Dublin12, University of Alberta13, University of Adelaide14, Queen's University15, Ottawa Hospital Research Institute16, University of Ottawa17, University of Melbourne18, Royal Adelaide Hospital19, Royal Cornwall Hospital20
TL;DR: Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression.
Abstract: Background Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer. Methods In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events. Results A total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P = 0.002). Kaplan-Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P Conclusions Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel. (Funded by Astellas Scientific and Medical Affairs and others; ENZAMET (ANZUP 1304) ANZCTR number, ACTRN12614000110684; ClinicalTrials.gov number, NCT02446405; and EU Clinical Trials Register number, 2014-003190-42.).