Cost-effectiveness analysis of cabazitaxel for metastatic castration resistant prostate cancer after docetaxel and androgen-signaling-targeted inhibitor resistance.

BACKGROUND: The aim of our study was to evaluate the cost-effectiveness of cabazitaxel versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel who had progression within 12 months while receiving an alternative inhibitor (abiraterone or enzalutamide) from a US payer's perspective. METHODS: To conduct the cost-effectiveness analysis, a Markov decision model was established. Three health states (progression-free survival (PFS), progressive disease (PD) and death) were included, and the incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint. The willingness-to-pay (WTP) threshold was set at $100,000.00/quality-adjusted life year (QALY), and discounted rates were set at 3% annually. Efficacy data were derived from the CARD trial and Weibull distribution curves were modeled to fit the survival curves. The robustness of the analysis was tested with a series of one-way sensitivity analyses and probabilistic sensitivity analyses. RESULTS: Overall, the incremental effectiveness and cost of cabazitaxel versus androgen-signaling-targeted inhibitors (ASTIs) were 0.16 QALYs and $49,487.03, respectively, which yielded an ICER of $309,293.94/QALY. Our model was mostly sensitive to the duration of PFS in the cabazitaxel group, cost of cabazitaxel and utility of the PFS state. At a WTP threshold of $100,000.00/QALY, cabazitaxel was the dominant strategy in 0% of the simulations. CONCLUSIONS: Cabazitaxel is unlikely to be a cost-effective treatment option compared with ASTIs in patients with mCRPC previously treated with docetaxel who had progression within 12 months while receiving ASTIs.

Adherence and out-of-pocket costs among Medicare beneficiaries who are prescribed oral targeted therapies for advanced prostate cancer.

BACKGROUND: Abiraterone and enzalutamide are high-cost oral therapies that increasingly are used to treat patients with advanced prostate cancer; these agents carry the potential for significant financial consequences to patients. In the current study, the authors investigated coping and material measures of the financial hardship of these therapies among patients with Medicare Part D coverage. METHODS: The authors performed a retrospective cohort study on a 20% sample of Medicare Part D enrollees who underwent treatment with abiraterone or enzalutamide between July 2013 and June 2015. The authors described the variability in adherence rates and out-of-pocket payments among hospital referral regions in the first 6 months of therapy and determined whether adherence and out-of-pocket payments were associated with patient factors and the socioeconomic characteristics of where a patient was treated. RESULTS: There were 4153 patients who filled abiraterone or enzalutamide prescriptions through Medicare Part D in 228 hospital referral regions. The mean adherence rate was 75%. The median monthly out-of-pocket payment for abiraterone and enzalutamide was $706 (range, $0-$3505). After multilevel, multivariable adjustment for patient and regional factors, adherence was found to be lower in patients who were older (69% for patients aged ≥85 years vs 76% for patients aged <70 years; P < .01) and in those with low-income subsidies (69% in those with a subsidy vs 76% in those without a subsidy; P < .01). Both Hispanic ethnicity and living in a hospital referral region with a higher percentage of Hispanic beneficiaries were found to be independently associated with higher out-of-pocket payments for abiraterone and enzalutamide. CONCLUSIONS: There were substantial variations in the adherence rate and out-of-pocket payments among Medicare Part D beneficiaries who were prescribed abiraterone and enzalutamide. Sociodemographic patient and regional factors were found to be associated with both adherence and out-of-pocket payments.

Effectiveness and safety assessment of drospirenone/ethinyl estradiol tablet in treatment of PCOS patients: a single center, prospective, observational study.

BACKGROUND: To investigate the effectiveness and safety of 3 mg drospirenone and 20 µg ethinyl estradiol tablet (3 mg DRSP/20 µg EE) in the treatment of polycystic ovary syndrome (PCOS). METHODS: This single center, prospective observational study was conducted in 140 patients with PCOS. They were prescribed 3 mg DRSP/20 µg EE in a 24/4/ regimen for 3 months. Patients were instructed to take oral DRSP/EE tablets (once daily) on the 2nd day of menstruation, for 28 consecutive days for 1 cycle. After 3 months of treatment, anthropometric assessments along with variations in sex hormones related index, glucolipid metabolic index, changes in bilateral ovarian volume, as well as adverse effect of the combination were evaluated. RESULTS: When compared to baseline, body mass index (BMI, 22.07 ± 4.09 vs. 21.35 ± 3.22, p < 0.001) and waist hip ratio (WHR, 0.86 ± 0.07 vs. 0.854 ± 0.06, p = 0.026) decreased significantly after treatment. Sex-hormones such as luteinizing hormone (LH) (10.88 vs. 5.81 U/L), testosterone (T) (1.85 vs. 1.51 nmol/L) and free androgen index (FAI) (5.37 vs. 1.50) decreased significantly after treatment (p < 0.001). Follicular stimulating hormone (FSH) increased significantly at 3 months as compared to before treatment (5.13 vs. 5.42 U/L, p = 0.009). Plasma insulin (11.03 vs. 11.10 pmol/L), fasting (4.97 vs. 4.93 mmol/L) and 2 h-blood glucose levels (7.18 vs. 7.04 mmol/L) did not change when compared to baseline. Plasma triglycerides (TG, 1.32 vs. 1.65 mmol/L) significantly increased 3 months after treatment when compared to before treatment (p < 0.001). However, high density lipoprotein-cholesterol (HDL-C) levels increased significantly after treatment (1.41 vs. 1.57 mmol/L, p < 0.001). It was seen that, when compared to baseline, bilateral ovarian volume (left and right) was significantly lower after treatment (p < 0.05). It was seen that 81 patients reported no adverse reactions. Of the common discomforts reported, breast swelling and pain, gastrointestinal disorder and dizziness and headache were most frequent. CONCLUSIONS: Treatment of PCOS patients with3 mg DRSP/20 µg EE has shown beneficial hormonal and lipid profile along with considerable safety profile. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900022001, March 2019, retrospectively registered.

Metastatic Hormone-Sensitive Prostate Cancer: A Review of the Current Treatment Landscape.

PURPOSE: In recent years, the treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) have expanded significantly. In addition to androgen deprivation therapy, the systemic treatments now include docetaxel, abiraterone, enzalutamide, and apalutamide. Radiation to the primary is also an option for select low-volume patients. METHODS: We conducted a review of the pivotal trials that have changed the practice of mHSPC. RESULTS: We describe an overview of the trials that investigated docetaxel (CHAARTED and STAMPEDE-Docetaxel), abiraterone (LATTITUDE and STAMPEDE-Abiraterone), enzalutamide (ARCHES, ENZAMET), apalutamide (TITAN), and radiation to the primary (STAMPEDE-Radiation). DISCUSSION: The treatment of mHSPC is a complex topic, and treatment choice should be individualized. Patient preferences, cost, volume of disease, and side effect profiles are important in determining which option is the best for an individual patient.

Long-term clinical impact of PSA surge in castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. PATIENTS AND METHODS: We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses. RESULTS: A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge. CONCLUSION: PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon.

Drospirenone-Containing Oral Contraceptive Pills and the Risk of Venous Thromboembolism: An Assessment of Risk in First-Time Users and Restarters.

INTRODUCTION: The effects of drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) remain controversial due to the challenge in distinguishing between first-time users and restarters, and their different underlying VTE risks, in healthcare databases. OBJECTIVES: The aim of this study was to describe the challenge of studying the risk of VTE among first-time users of drospirenone-containing COCs in a healthcare database and assess the risk among first-time users and restarters. METHODS: We used data from the Clinical Practice Research Datalink to construct two cohorts. The first-time user cohort included all women aged 16-45 years who received a first ever prescription of drospirenone- or levonorgestrel-containing COCs between May 2002 and March 2015. The restarter cohort included those who were restarting a COC after a period of non-use of ≥6 months. Cox proportional hazards models adjusted for high dimensional propensity scores were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The final cohorts included 55,139 first-time users (3582 drospirenone and 51,557 levonorgestrel) and 162,959 restarters (23,191 drospirenone and 139,768 levonorgestrel). The adjusted HR of VTE associated with drospirenone versus levonorgestrel was 3.19 (95% CI 1.12-9.08) for first-time users and 1.96 (95% CI 1.12-3.41) for restarters. CONCLUSIONS: We found an elevated risk of VTE associated with drospirenone-containing COCs in comparison with levonorgestrel-containing COCs in both cohorts. While left truncation of healthcare databases is a concern for the identification of first-time users, the use of a more explicit cohort of restarters suggests a doubling of VTE risk with drospirenone-containing COCs.

Docetaxel chemotherapy in metastatic castration-resistant prostate cancer: cost of care in Medicare and commercial populations.

OBJECTIVE: To estimate the healthcare costs and characteristics of docetaxel chemotherapy episodes of care for men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: This study used the Medicare 5% sample and MarketScan Commercial (2010-2013) claims data sets to identify men with mCRPC and initial episodes of docetaxel treatment. Docetaxel episodes included docetaxel claim costs from the first claim until 30 days after the last claim, with earlier termination for death, insurance disenrollment, or the end of a 24-month look-forward period from initial docetaxel index date. Docetaxel drug claim costs were adjusted for 2011 generic docetaxel introduction, while other costs were adjusted to 2015 values using the national average annual unit cost increase. RESULTS: This study identified 281 Medicare-insured and 155 commercially insured men, with 325 and 172 docetaxel episodes, respectively. The average number of cycles (unique docetaxel infusion days) per episode was 6.9 for Medicare and 6.3 for commercial cohorts. The average cost per episode was $28,792 for Medicare and $67,958 for commercial cohorts, with docetaxel drug costs contributing $2,588 and $13,169 per episode, respectively. The average cost per episode on docetaxel infusion days was $8,577 (30%) for Medicare and $28,412 (42%) for commercial. Non-docetaxel infusion day costs included $7,074 (25%) for infused or injected drugs for Medicare, $10,838 (16%) for commercial cohorts, and $6,875 (24%) and $9,324 (14%) for inpatient admissions, respectively. LIMITATIONS: The applicability is only to the metastatic castration-resistance clinical setting, rather than the metastatic hormone-sensitive setting, and the lack of data on the cost effectiveness of different sequencing strategies of a range of systemic therapies including enzalutamide, abiraterone, radium-223, and taxane chemotherapy. CONCLUSION: The majority of docetaxel episode costs in Medicare and commercial mCRPC populations were non-docetaxel drug costs. Future research should evaluate the total cost of care in mCPRC.

Abiraterone for castration-resistant prostate cancer: adherence, survival and hospitalization : Analysis of a medical claims database.

OBJECTIVE: To analyze the drug adherence rates and overall survival for in patients treated with arbiraterone acetate (AA) for castration-resistant prostate cancer (CRPC). METHODS: The database of the largest insurance company in Austria (Wiener Gebietskrankenkasse) was analyzed. Data on all CRPC patients with at least one prescription of AA between November 2011 and December 2014 in the postchemotherapy setting were collated and compared to the Austrian death and hospital admission statistics. Drug adherence was estimated by the medication possession ratio (MPR). RESULTS: Data of 270 patients (mean age 73.5 ± 8.9 years) were analyzed. The mean duration of AA treatment was 9.8 months (range 1-38 months). The duration of AA treatment was as follows: 0-2 months 53 patients (19.6 %), 3-5 months 73 patients (28.1 %), 6-10 months 67 patients (24.8 %) and >10 months 97 patients (35.9 %). The median MPR was 100 % and in 241 (89.2 %) the MPR exceeded ≥80 %. The median overall survival (OS) was 11 months. Based on Kaplan-Meier analysis, the 6 month OS was 61 %, 12 month OS 43 %, 18 month OS 35 % and >24 month OS 24 %. The OS was strongly correlated to patient age and the duration of AA treatment. Of all 270 patients, only 19 (7 %) were not hospitalized during their remaining life span and 71 (26.2 %) spent more than 50% of their remaining life span in hospital care. CONCLUSION: The OS was shorter than in phase III trials and strongly correlated to patient age and the duration of AA treatment. The high mortality rate within the first 6 months of AA treatment in this real-life setting suggests a less stringent patient selection than in a phase III trial.

Continuous Norethisterone Acetate versus Cyclical Drospirenone 3 mg/Ethinyl Estradiol 20 µg for the Management of Primary Dysmenorrhea in Young Adult Women.

STUDY OBJECTIVE: To evaluate the efficacy of continuous norethisterone acetate (NET-A), 5 mg (group N) vs cyclical combined oral contraceptive pill (COC) consisting of drospirenone 3 mg/ethinyl estradiol 20 µg pills (group P) in treating dysmenorrhea in young adult women. DESIGN, SETTING, AND PARTICIPANTS: This prospective, open-label, nonrandomized study included 38 Jordanian patients: 20 patients in group N and 18 patients in group P. INTERVENTIONS: Continuous NET-A 5 mg daily or cyclical COC. MAIN OUTCOME MEASURES: Pain scores, adverse effects, analgesic use, school absence, and cost. RESULTS: Thirty-eight patients used NET-A or COC for 6 months. All participants had almost the same starting levels of visual analogue scale (VAS) scores. Both drugs were similar in suppressing dysmenorrhea at the 3-month follow-up visit; VAS score mean (±SD) in group N and P were 1.30 ± 1.22 and 1.28 ± 0.83 (P = .22), respectively, and after 6 months, with mean VAS scores (±SD) of 1.30 ± 1.22 and 1.28 ± 0.83, respectively (P = .95). The cost of the treatment in the N group was much less than in the P group. Participants in the N group were less likely to use pain killers: 20% and 44% in the N and P groups, respectively (P = .006) in the first month and only 5% and 17% (P = .019) in the N and P groups, respectively, at the 3-month follow-up, and none of them used any analgesics at the 6-month follow-up. CONCLUSION: A continuous NET-A regimen is a well tolerated, effective, and inexpensive option for dysmenorrhea treatment and was as good as COC.

In with the new: the determinants of prescribing innovation by general practitioners in Ireland.

An important element of the process by which new drugs achieve widespread use is their adoption by GPs. In this paper, we explore the factors that shape the timing of the first prescription of six new drugs by General Practitioners in Ireland. Our analysis is based on a dataset that matches prescription data with data on GP characteristics. We then use duration analysis to explore both equilibrium and non-equilibrium determinants of prescribing innovation. Our study highlights a range of commonalities across all of the drugs considered and suggests the importance of GP and practice characteristics in shaping prescribing decisions. We also find strongly significant, and consistently signed, stock and order effects across these drugs: GPs who have a track record of early adoption tend also to be early adopters of other new drugs; and, the larger the proportion of GPs which have already adopted a new drug the slower is subsequent adoption. Epidemic and learning effects are also evident with slower adoption by rural practices and among those GPs with narrower prescribing portfolios.

Long-term assessment of symptomatology and satisfaction of an extended oral contraceptive regimen.

OBJECTIVE: The study was conducted to assess hormone withdrawal symptoms, patient acceptance and occurrence and management of bleeding with an extended oral contraceptive (OC) regimen. METHODS: Subjects were placed on an OC containing 3 mg drosperinone (DRSP) and 30 microg ethinyl estradiol (EE), in the standard 21/7 fashion for two cycles, before converting to an extended pattern of OC for women who indicated they had menstrually related symptoms such as headaches, cramping and mood swings (52 weeks with phone-call follow-up 6 months later). Daily assessments of bleeding, headache, pelvic pain, mood and number of pain pills were recorded. Results are reported as means with S.E., and values were compared using analysis of variance with Dunnett's post hoc test for comparison with 21/7 cycle, Duncan's post hoc test for comparison of changes during the course of the extended regimen and Pearson's chi-square for comparison of proportions. RESULTS: Of the 111 women who began the extended OC regimen, 80 completed 1 year of use. Mood scores, headache scores and pelvic pain were all improved in the extended OC intervals, compared to the 21/7 cycle (p<.001 for all comparisons). Improvement in symptoms persisted throughout the 1 year extended regimen. The findings indicated that 53.7% of subjects had no breakthrough bleeding or breakthrough spotting (BTB/BTS) during any given 28-day interval of the extended regimen. BTB/BTS decreased in the second half compared to the first half of the extended regimen. To manage BTB/BTS, instituting a 3-day hormone-free interval (HFI) was significantly more effective than continuing OCs (p<.001). At the 6-month follow-up, most subjects had continued the extended regimen on their own with a high level of satisfaction. CONCLUSIONS: An extended OC regimen containing DRSP/EE significantly improved mood, headaches and pelvic pain scores throughout the 1 year of use, compared to a 21/7 cycle. Sustained BTB/BTS episodes occurred in 45 subjects (56%), decreasing in the second half of the study and effectively managed with a 3-day HFI.

Serum potassium monitoring for users of ethinyl estradiol/drospirenone taking medications predisposing to hyperkalemia: physician compliance and survey of knowledge and attitudes.

PURPOSE: Yasmin-28 [ethinyl estradiol 0.03 mg/drospirenone 3 mg (EE/DRSP)] contains drospirenone, a progestin component that possesses antimineralocorticoid activity with a potassium-sparing diuretic effect similar to that in spironolactone. Product labeling recommends potassium monitoring in the first month of use for women concurrently receiving medication that may increase serum potassium. METHODS: We evaluated compliance with this recommendation by measuring monitoring around the date of oral contraceptive (OC) initiation in women who received EE/DRSP while being treated with medications predisposing to hyperkalemia and in similar women who received other OCs. Because preliminary analyses indicated incomplete compliance, we surveyed physicians who prescribed EE/DRSP to women receiving drugs predisposing to hyperkalemia on their knowledge and attitudes with regard to the recommendation. We conducted this study using data from the Ingenix Research Datamart, which includes insurance claims for reimbursement for medical services and prescription medications for approximately 8,000,000 members of a large nationally dispersed health plan. We used claims for pharmacy dispensings of prescription medications to identify all women aged 10-59 years old who initiated EE/DRSP or other OCs during the first 3 years of EE/DRSP availability (July 2001 to June 2004). The frequency of potassium monitoring was measured by identifying claims for serum potassium tests. We conducted a telephone survey of 58 physicians who had prescribed EE/DRSP up to June 2003 to women who received concomitant hyperkalemic drugs. RESULTS: Although potassium monitoring was generally more frequent among EE/DRSP initiators receiving concomitant hyperkalemic drugs than among other OC initiators receiving similar medications, only 40% of 466 EE/DRSP initiators with concurrent hyperkalemic treatment had potassium tests. More than 98% of surveyed physicians were aware of the potassium-sparing property of EE/DRSP. Compared with physicians whose patients had potassium tests, physicians of patients without such tests were more likely to disagree with the recommendation for users of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, heparin and nonsteroidal anti-inflammatory drugs. Patient barriers and health plan restrictions were other factors possibly contributing to noncompliance. CONCLUSION: This study demonstrates incomplete physician compliance with a labeling recommendation of potassium monitoring for initiators of EE/DRSP receiving concomitant therapy predisposing to hyperkalemia. The limited compliance was likely due to a combination of selective physician acceptance of the recommendations and specific patient and health plan barriers to testing.