PURPOSE:The Medtronic implantable tibial neuromodulation system is a leadless, rechargeable, minimally invasive option intended to treat the symptoms of urge urinary incontinence (UUI), a common condition that significantly impairs quality of life. TITAN 2 is a pivotal study evaluating safety and effectiveness of the Medtronic implantable tibial neuromodulation system. The results through 12 months are reported. MATERIALS AND METHODS:This prospective, multicenter, single-arm investigational device exemption study enrolled eligible overactive bladder subjects with UUI. The primary end point was the percentage of subjects who had ≥ 50% reduction in UUI episodes/day after 6 months. Safety was characterized as the rate of adverse device effects (ADEs). Data are reported as mean ± SD or with 95% CIs. RESULTS:Of 126 implanted subjects, 95% were female, the mean age was 63 ± 14 years, and BMI was 35 ± 9 kg/m2. The primary objective was met with 59% of subjects achieving ≥ 50% improvement in UUI episodes/day (95% CI: 49%-67%, P < .0001) at 6 months; at 12 months, 61% had ≥ 50% improvement. Change from baseline was statistically significant at 6 months for UUI episodes/day, voids/day (in urinary frequency subjects), and Urgency Perception Score, with improvements in all 3 symptoms maintained through 12 months. Twenty percent of subjects experienced ADEs through 12 months; 1 ADE was serious and was recovered/resolved. CONCLUSIONS:TITAN 2 met the primary and all secondary objectives by showing a statistically significant improvement of UUI, urinary frequency, and urgency symptoms. Clinical benefits and a favorable safety profile were maintained through 12 months.
BACKGROUND:Patients with metastatic hormone-sensitive prostate cancer (mHSPC) require long-term treatment to delay progression and improve survival, while minimizing adverse events or negative impact on symptoms (e.g. pain) and health-related quality of life (HRQoL). In ARASENS (NCT02799602), darolutamide plus androgen deprivation therapy (ADT) and docetaxel significantly improved overall survival (primary endpoint) versus placebo plus ADT and docetaxel. We report clinically relevant endpoints and HRQoL in ARASENS. METHODS:Patients with mHSPC were randomized to darolutamide 600 mg orally twice daily or placebo, with ADT and docetaxel. Outcomes of interest were times to metastatic castration-resistant prostate cancer (mCRPC), pain progression, worsening of Brief Pain Inventory-Short Form pain interference/severity, and worsening of National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy Prostate Cancer Symptom Index 17-item questionnaire (NFPSI-17) scores. RESULTS:In 1305 patients analyzed (darolutamide 651, placebo 654), darolutamide significantly delayed time to mCRPC (hazard ratio 0.36 [95 % confidence interval 0.30-0.42]) and time to pain progression (0.79 [0.66-0.95]) versus placebo. Times to worsening of pain interference/severity and NFPSI-17 scores were similar between treatment groups. Incidences of treatment-emergent adverse events (TEAEs) commonly associated with androgen receptor pathway inhibition were generally low and similar between groups (median follow-up: > 3.5 years). CONCLUSION:Darolutamide plus ADT and docetaxel provided significant benefits in clinically relevant endpoints versus ADT and docetaxel, with similar control of pain, maintenance of HRQoL, and no cumulative TEAEs over long-term treatment. These data reinforce darolutamide triplet therapy as a standard-of-care treatment option in patients with mHSPC.
IMPORTANCE:There are significant deficiencies in the general population's knowledge of pelvic floor disorders, including pelvic organ prolapse (POP). Educational videos can equip patients with a better understanding of POP. OBJECTIVES:The objectives of this study were to assess whether a previsit POP educational video improves patient satisfaction with their management decision. Secondary outcomes were POP knowledge, patient perception of knowledge, decision conflict, physician perception of patient comprehension, and counseling ease. STUDY DESIGN:This was a physician-blinded, randomized trial. Thirty-seven participants with POP symptoms were assigned to watch a previsit video (video group, n=18) or no video (control group, n=19). Eligibility included age 18 years or older, initial POP evaluation, English-speaking, internet access, and no prior POP treatment, pregnancy, or cognitive disability. Participants completed a baseline, postvisit, and postmanagement survey, which included the Prolapse and Incontinence Knowledge-POP Questionnaire (PIKQ-POP), a self-assessment of POP knowledge, the Satisfaction with Decision Scale for Pelvic Floor Disorders (SDS-PFD), and decision conflict questions. The counseling physicians were surveyed on their perceptions of patient comprehension and counseling ease. RESULTS:After the initial visit, mean SDS-PFD scores were similar (4.89 vs. 4.78; P=0.44). However, the change in PIKQ-POP scores was greater in the video group (2.69 vs. 1.13; P=0.03). The change in self-perception of POP knowledge was also greater in the video group (1.72 vs. 1.05, P=0.02). There were no major differences in decision conflict, physician counseling ease, or perception of patient comprehension. CONCLUSIONS:POP video education as a supplemental resource to health care provider counseling did not improve patient decision satisfaction. It may improve POP knowledge from baseline though this study was not powered for this outcome.
BACKGROUND:In the phase 3 EMBARK trial, enzalutamide plus leuprolide and enzalutamide monotherapy were associated with longer metastasis-free survival than leuprolide alone among patients with biochemically recurrent prostate cancer. The final analysis of overall survival has not been reported. METHODS:We randomly assigned patients with prostate cancer who had high-risk biochemical recurrence in a 1:1:1 ratio to receive enzalutamide plus leuprolide (the combination group), leuprolide alone (the leuprolide-alone group), or enzalutamide monotherapy (the monotherapy group). The primary end point was metastasis-free survival, assessed in the combination group as compared with the leuprolide-alone group. Overall survival was an alpha-controlled, key secondary end point. Updated results for prespecified secondary end points, including the time to first use of new antineoplastic therapy and the time to the first symptomatic skeletal event, were summarized descriptively, as was progression-free survival with the first subsequent therapy, an exploratory end point. RESULTS:The 8-year overall survival was 78.9% (95% confidence interval [CI], 73.9 to 83.1) in the combination group and 69.5% (95% CI, 64.0 to 74.3) in the leuprolide-alone group; the hazard ratio for death was 0.60 (95% CI, 0.44 to 0.80; P<0.001). The 8-year overall survival with monotherapy was 73.1% (95% CI, 67.6 to 77.9), which did not differ significantly from that with leuprolide alone (hazard ratio, 0.83; 95% CI, 0.63 to 1.10; P = 0.19). In the descriptive updates for prespecified secondary end points, results were similar to those previously reported. Safety findings were consistent with those in the primary analysis of metastasis-free survival. CONCLUSIONS:Overall survival was significantly longer with the combination of enzalutamide and leuprolide than with leuprolide alone among patients with prostate cancer with high-risk biochemical recurrence. Enzalutamide monotherapy was not superior to leuprolide alone in the analysis of overall survival. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).
