Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer.

BACKGROUND: In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Here we report the results of a protocol-specified second interim analysis of overall survival. METHODS: Patients were randomly assigned in a 2:1 ratio to receive either ribociclib or placebo in addition to fulvestrant as first-line or second-line treatment. Survival was evaluated by means of a stratified log-rank test and summarized with the use of Kaplan-Meier methods. RESULTS: This analysis was based on 275 deaths: 167 among 484 patients (34.5%) receiving ribociclib and 108 among 242 (44.6%) receiving placebo. Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant. The estimated overall survival at 42 months was 57.8% (95% confidence interval [CI], 52.0 to 63.2) in the ribociclib group and 45.9% (95% CI, 36.9 to 54.5) in the placebo group, for a 28% difference in the relative risk of death (hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.00455). The benefit was consistent across most subgroups. In a descriptive update, median progression-free survival among patients receiving first-line treatment was 33.6 months (95% CI, 27.1 to 41.3) in the ribociclib group and 19.2 months (95% CI, 14.9 to 23.6) in the placebo group. No new safety signals were observed. CONCLUSIONS: Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant in patients with hormone-receptor-positive, HER2-negative advanced breast cancer. (Funded by Novartis; MONALEESA-3 ClinicalTrials.gov number, NCT02422615.).

Patient-centered applications: use of information technology to promote disease management and wellness. A white paper by the AMIA knowledge in motion working group.

Advances in information technology (IT) enable a fundamental redesign of health care processes based on the use and integration of electronic communication at all levels. New communication technologies can support a transition from institution centric to patient-centric applications. This white paper defines key principles and challenges for designers, policy makers, and evaluators of patient-centered technologies for disease management and prevention. It reviews current and emerging trends; highlights challenges related to design, evaluation, reimbursement and usability; and reaches conclusions for next steps that will advance the domain.

Meta-analysis of ablation of atrial flutter and supraventricular tachycardia.

The purpose of this study was to perform a systematic review and meta-analysis to evaluate the safety and efficacy of radiofrequency ablation (RFA) of typical atrial flutter (AFL) and atrioventricular node-dependent supraventricular tachycardia (SVT) in adult patients. Medline and EMBASE were searched (1990 to 2007) for all study design trials of RFA. Data relating to single- and multiple-procedure success, arrhythmia recurrence, repeat ablation, adverse events, and death were extracted. For RFA in AFL, 18 primary studies with 22 treatment arms and 1,323 patients were identified. Single-procedure success for AFL was 91.7% (95% confidence interval [CI] 88.4% to 94.9%). Multiple-procedure success was 97.0% (95% CI 94.7% to 99.4%). Postablation arrhythmia was noted in 13.2% of patients (95% CI 7.5% to 18.9%), while repeat ablation was reported in 8% (95% CI 4.5% to 11.4%). For RFA of SVT, 39 primary studies with 49 treatment arms in 7,693 patients with accessory pathways and atrioventricular nodal reentrant tachycardia were identified. Single-procedure success for SVT was 93.2% (95% CI 90.8% to 95.5%). Multiple-procedure success was 94.6% (95% CI 92.4% to 96.9). Postablation arrhythmia was noted in 5.6% patients (95% CI 4.1% to 7.2%). Repeat ablation occurred in 6.5% (95% CI 4.7% to 8.3%). For AFL studies, all-cause mortality was 0.6%, and adverse events were reported in 0.5% of patients. For SVT studies, all-cause mortality was 0.1%, and adverse events were reported in 2.9% of patients. In conclusion, studies of RFA for the treatment of patients with AFL and SVT report high efficacy rates and low rates of complications.

Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses.

BACKGROUND: Although radiofrequency catheter ablation (RFA) has evolved from an experimental procedure to an important treatment option for atrial fibrillation, the relative safety and efficacy of catheter ablation relative to that of antiarrhythmic drug (AAD) therapy has not been established. METHODS AND RESULTS: Two separate systematic reviews were conducted: one on RFA and the other on AAD to provide accurate and broadly representative estimates of the clinical efficacy and safety of both therapies in the treatment of atrial fibrillation. Electronic searches were conducted in EMBASE and MEDLINE from 1990 to 2007. For the RFA review, all study designs were accepted. For the AAD review, articles were limited to prospective studies on the following drugs of interest: amiodarone, dofetilide, sotalol, flecainide, and propafenone. Data were extracted by 1 reviewer, with a second reviewer performing independent confirmation of extracted data. Sixty-three RFA and 34 AAD studies were included in the reviews. Patients enrolled in RFA studies tended to be younger (mean age, 55 versus 62 years), had longer duration of atrial fibrillation (6.0 versus 3.1 years), and had failed a greater number of prior drug trials (2.6 versus 1.7). The single-procedure success rate of ablation off AAD therapy was 57% (95% CI, 50% to 64%), the multiple procedure success rate off AAD was 71% (95% CI, 65% to 77%), and the multiple procedure success rate on AAD or with unknown AAD usage was 77% (95% CI, 73% to 81%). In comparison, the success rate for AAD therapy was 52% (95% CI, 47% to 57%). A major complication of catheter ablation occurred in 4.9% of patients. Adverse events for AAD studies, although more common (30% versus 5%), were less severe. CONCLUSIONS: Studies of RFA for treatment of atrial fibrillation report higher efficacy rates than do studies of AAD therapy and a lower rate of complications.