Treatment and overall survival among anti-PD-1-exposed advanced melanoma patients with evidence of disease progression.

Background: Little is known regarding treatment patterns and overall survival (OS) for patients with advanced melanoma who progress after anti-PD-1 exposure. Methods: The Kaplan-Meier method was used to evaluate OS from electronic health records for patients with advanced melanoma who progressed on anti-PD-1 therapy and received subsequent therapy. Descriptive statistics were used to summarize treatment. Results: A total of 304 patients who progressed after anti-PD-1 therapy received subsequent therapy: 50% immunotherapy, 36% BRAF and/or MEK inhibitors, 14% other therapies. Median OS was 7.2 months (95% CI: 6.4-8.8), with an association (p < 0.01) with best response to baseline anti-PD-1 therapy and further associations with Eastern Co-operative Oncology Group (ECOG) performance status ≤1 (p < 0.001 compared with ECOG ≥2), normal LDH (p < 0.001 compared with elevated levels) and treatment with BRAF and/or MEK inhibitors (p = 0.02 compared with other treatment). There was an association (p < 0.01) of survival with best response to baseline anti-PD-1 therapy. Conclusions: OS for advanced melanoma patients who progress on anti-PD-1 therapy is suboptimal, which highlights the need for further research to develop new medications and optimize treatment strategies.

Vibegron (RVT-901/MK-4618/KRP-114V) Administered Once Daily as Monotherapy or Concomitantly with Tolterodine in Patients with an Overactive Bladder: A Multicenter, Phase IIb, Randomized, Double-blind, Controlled Trial.

BACKGROUND: Antimuscarinics have shown modest efficacy with unwanted side effects in patients with overactive bladder (OAB). Efficacy of vibegron, a new ß3-adrenergic receptor agonist, for OAB is unknown. OBJECTIVE: To evaluate the efficacy of once-daily oral vibegron in OAB patients (primary), and its safety, tolerability, and efficacy when administered alone or concomitantly with tolterodine (secondary). DESIGN, SETTING, AND PARTICIPANTS: International, phase IIb, randomized, double-blind, placebo- and active comparator-controlled, two-part superiority trial (2011-2013) in OAB-wet or OAB-dry patients aged 18-75 yr (NCT01314872). INTERVENTIONS: Part 1: once-daily oral vibegron monotherapy (3 [V3], 15 [V15], 50 [V50], or 100 [V100] mg), tolterodine extended release 4mg (TER4), or placebo for 8 wk, or combination V50/TER4 for 4 wk and then V50 for 4 wk; part 2: V100/TER4, V100, TER4, or placebo for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Average daily micturitions at week 8 of part 1 (primary); urge incontinence episodes, total incontinence episodes, and urgency episodes (secondary). RESULTS AND LIMITATIONS: Overall, 1395 patients were randomized. From baseline to week 8, V50 and V100 significantly decreased average daily micturitions (least square mean difference [95% confidence interval], -0.64 [-1.11, -0.18]; p=0.007 and -0.91 [-1.37, -0.44]; p<0.001, respectively) and the number of urge incontinence episodes (-0.72 [-1.11, -0.33] and -0.71 [-1.10, -0.32], respectively; both p<0.001) versus placebo. All vibegron doses were well tolerated. The incidence of dry mouth was higher with TER4 than with vibegron monotherapy. Results are limited by the relatively short treatment duration. CONCLUSIONS: Once-daily V50 and V100 improved OAB symptoms; vibegron was well tolerated as monotherapy and concomitantly with tolterodine. Further development is warranted. PATIENT SUMMARY: Antimuscarinics, commonly used to treat overactive bladder, produce modest efficacy and unwanted side effects. In this study, a different type of drug (vibegron) was efficacious and safe, alone or with an antimuscarinic (tolterodine).

Changes in diabetes medication regimens and glycemic control in adolescents and young adults with youth-onset type 2 diabetes: The SEARCH for diabetes in youth study.

OBJECTIVE: The aim of this study was to describe recent medication patterns and changes in medication patterns and glycemic control in adolescents and young adults with incident type 2 diabetes (T2D). METHODS: Using data from the SEARCH for Diabetes in Youth Study, we conducted a cross-sectional analysis of treatments for adolescents and young adults with incident T2D in 2 periods (2002-2005 vs 2008/2012), and a longitudinal analysis of medications and glycemic control for a subset with baseline and follow-up visits. Comparisons were performed using χ2 , Fisher's exact, or ANOVA. RESULTS: Of 646 individuals in the cross-sectional analysis, a majority in each period received metformin (64.9% vs 70.4%) and/or insulin (38.1% vs 38.4%), while fewer used sulfonylureas (5.6% vs 3.6%) with non-significant changes over time. There was a significant reduction in thiazolidinedione use (5.0% vs 2.0%, P < .05). In the longitudinal analysis, 322 participants were followed for 7 years, on average. Baseline metformin users had a lower A1C (6.4% [46.7 mmol/mol]) compared to insulin (8.4% [68.2 mmol/mol], P < .001) or insulin plus any oral diabetes medication (ODM) users (7.7% [60.4 mmol/mol], P < .001). Among baseline metformin users (n = 138), 29.7% reported metformin at follow-up, with the remainder adding (19.6%) or switching to insulin (8.0%), ODM (15.9%), or lifestyle only (26.8%). Of those receiving insulin (±ODM) (n = 129), 76% reported insulin use at follow-up. Overall, 35% were at A1C goal (<7.0%, 53 mmol/mol) at follow-up. CONCLUSIONS: Youth-onset T2D is still largely being treated with metformin and/or insulin. The majority treated were not at American Diabetes Association (ADA)-recommended goal 7 years after diagnosis.