Cardiovascular safety of mometasone/indacaterol and mometasone/indacaterol/glycopyrronium once-daily fixed-dose combinations in asthma:pooled analysis of phase 3 trials

OBJECTIVE: To evaluate cardiovascular safety of two new inhaled fixed-dose combinations for treatment of asthma: (i) the inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) mometasone furoate/indacaterol acetate (MF/IND), (ii) the ICS/LABA/long-acting muscarinic antagonist (LAMA) MF/IND/glycopyrronium bromide (GLY). METHODS: Patient-level data were pooled from four randomized trials, including 52-week studies PALLADIUM (n = 2216) and IRIDIUM (n = 3092), 24-week study ARGON (n = 1426), and 12-week study QUARTZ (n = 802). Cardio-/cerebrovascular (CCV) event frequencies were examined in the following comparisons: (1) LABA effect: pooled-dose MF/IND vs. pooled-dose MF; (2) LAMA effect: pooled-dose MF/IND/GLY vs. pooled-dose MF/IND; (3) ICS-dose effects: (a) high-dose MF/IND vs. medium-dose MF/IND, (b) high-dose MF/IND/GLY vs. medium-dose MF/IND/GLY; (4) intra-class effects: (a) high-dose MF/IND vs. Fluticasone/Salmeterol (F/S), (b) high-dose MF/IND/GLY vs. F/S + Tiotropium (TIO). Risk estimates (percentage of patients with ≥1 CCV event) and risk differences (RDs) with 95% confidence intervals (CIs) were calculated for each comparison. RESULTS: The frequency of CCV events was low, without notable differences between comparison groups. Risk estimates and corresponding RDs (95% CIs) were as follows: (1) pooled-dose MF/IND = 2.35%, pooled-dose MF = 2.18%, RD = 0.17% (-1.00%, 1.34%); (2) pooled-dose MF/IND/GLY = 3.65%, pooled-dose MF/IND = 3.77%, RD = -0.12% (-1.63%, 1.39%); (3a) high-dose MF/IND = 3.69%, medium-dose MF/IND = 3.35%, RD = 0.34% (-1.25%, 1.94%); (3b) high-dose MF/IND/GLY = 2.84%, medium-dose MF/IND/GLY = 2.02%, RD = 0.82% (-0.49%, 2.13%); (4a) high-dose MF/IND = 3.69%, F/S = 2.82%, RD = 0.87% (-0.66%, 2.40%); (4b) high-dose MF/IND/GLY = 1.26%, F/S + TIO = 1.05%, RD = 0.21% (-1.26%, 1.68%). CONCLUSIONS: There was no evidence of increased cardiovascular risk attributable to the addition of IND to MF or addition of GLY to MF/IND. Similarly, no evidence of increased cardiovascular risk was observed with an increase in the ICS-dose or relative to F/S ± TIO

Targeting the androgenic pathway in elderly patients with castration-resistant prostate cancer: A meta-analysis of randomized trials

BACKGROUND: The novel hormonal drugs have recently entered in the armamentarium of therapies for treatment of metastatic castration-resistant prostate cancer (CRPC). First reports are available for their use in elderly men with CRPC. METHOD: A meta-analysis of randomized controlled trials (RCTs) has been performed. PubMed, the Cochrane Library, and American Society of Clinical Oncology (ASCO) University Meeting were searched for data on the use of new hormonal treatment in elderly patients with CRPC. RESULTS: Nine studies for a total of 3512 elderly patients were available for meta-analysis. Six studies reported outcomes of patients aged >75 years old while 2 studies reported on patients aged >70 years old. The pooled analysis of the androgen synthesis inhibitors revealed significantly increased overall survival (OS) due to antiandrogen agents compared with placebo or placebo and prednisone (hazard ratio (HR) for death: HR = 0.74, 95% CI: 0.67-0.82; P\u200a<\u200a0.00001). Moreover, the new antiandrogenic therapy significantly improved the progression-free survival (HR = 0.45, 95% CI: 0.31-0.65; P\u200a<\u200a0.0001). The incidence of any grade 653 adverse effect was only moderately higher during with the antiandrogenic therapy as compared to the control arms (response rate = 1.03, 95% CI: 0.88-1.20; P = 0.72). CONCLUSION: This study confirmed that agents targeting the androgen axis (i.e., enzalutamide, abiraterone) significantly prolonged OS in elderly men with CRP