Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial.

PURPOSE: To compare NFOSI-18 Disease Related Symptoms - Physical (DRSP), Total score, and side effect bother between maintenance rucaparib (600 mg twice daily) vs. placebo in the phase III ARIEL3 trial. METHODS: ARIEL3 (NCT01968213) included patients with ovarian carcinoma who responded to second-line or later platinum-based chemotherapy. The NFOSI-18 DRS-P and Total scales were secondary endpoints. The NFOSI-18 contains a side effect impact item (GP5): "I am bothered by side effects of treatment." We compared treatment arms on change from baseline of DRS-P and Total scores using mixed models with repeated measures (MRMM). Time to first and confirmed deterioration of NFOSI-18 DRS-P and Total scales were analyzed using Cox regression. We also calculated the proportion of patients reporting moderate to high side effect bother on GP5. RESULTS: In the intention-to-treat (ITT) cohort, mean change from baseline favored the placebo. Compared to placebo, rucaparib was associated with higher risk of deterioration [e.g., 4-point deteriorator definition hazard ratio (HR): 1.85; 95% CI: 1.46, 2.36; median time to first deterioration on DRSP: 1.9 vs. 7.0 months]. Confirmed deterioration results resembled those for first deterioration. Proportions of patients reporting moderate/high side effect bother on GP5 fluctuated around 20% across treatment cycles. Results in BRCA mutant and homologous recombination deficient cohorts were generally similar to those from the ITT cohort. CONCLUSION: This placebo-controlled study in the maintenance therapy setting provides a unique view of the impact of PARP inhibition on the patient-reported outcomes that are commonly used in ovarian cancer clinical trials. Information regarding the adverse side effect impact of PARP inhibitors should be weighed against their clinical benefit.

Increasing prevalence of metastatic castration-resistant prostate cancer in a managed care population in the United States.

PURPOSE: Numerous treatment breakthroughs for patients with metastatic castration-resistant prostate cancer (mCRPC) have been demonstrated in clinical trials in the past 15 years. However, real-world evidence on the changing epidemiology and longevity of this population has not been demonstrated. This study assessed prevalence trends for mCRPC over eight years in a large managed care population. METHODS: In a claims database, adult male patients were included with ≥ 1 claim for prostate cancer, pharmacologic/surgical castration, and metastatic disease during the identification period. The index mCRPC date was the first metastatic claim; six months of continuous enrollment before and after was required. Patients with metastatic disease at baseline were excluded. Patients were followed until death, end of study, or disenrollment, whichever was earliest. Total, mCRPC per-prostate cancer, and age-specific prevalence rates were calculated cross-sectionally for each year under study (2010-2017). RESULTS: Of 343,089 patients identified with a claim for prostate cancer, 3690 mCRPC cases (1.1%) were identified. Incidence (new cases per year) remained relatively constant over the study period while prevalence of mCRPC (total cases per year) increased. mCRPC prevalence increased with increasing age. Total and mCRPC per-prostate cancer prevalence rates increased in monotonic, year-over-year trends from 2010 to 2017, while incidence (new cases per year) of mCRPC remained relatively stable. CONCLUSION: This study found increasing prevalence of mCRPC in an insured patient population during the 8-year period, coupled with stable incidence, validating that patients with the disease are living longer. With the addition of androgen receptor-directed therapies and poly(ADP-ribose) polymerase inhibitors in recent years, this trend will likely continue.

The Budget Impact of Including Rucaparib on a US Payer Formulary for the Treatment of Patients with Metastatic Ovarian Cancer.

OBJECTIVE: A budget impact model was constructed to assess the incremental budget impact that rucaparib availability would have on a US health plan. METHODS: An incremental budget impact was estimated over a 3-year horizon as the difference in total annual cost of treatment, with and without rucaparib available, for second-line maintenance, third-line treatment, and the combined maintenance and treatment settings. The hypothetical health plan includes one million covered lives, and commercial and Medicare lines of business. Alternative products included in the model were based on the National Comprehensive Cancer Network guidelines. The eligible patient population was estimated using an incidence-based approach. Modeled costs include drug acquisition, intravenous drug administration, required laboratory testing, and medical management of adverse events. RESULTS: In the maintenance setting, average total expenditures over 3 years were estimated to be US$1,465,043 with rucaparib versus US$1,461,350 without it as a treatment option; the average incremental budget impact was US$3693 (US$0.0003 per member per month [PMPM]). In the treatment setting, average total expenditures were estimated to be US$1,320,718 with rucaparib versus US$1,313,736 without it; the average incremental budget impact was US$6982 (US$0.0006 PMPM). Budget impact is smaller in commercial plans than Medicare because of the higher incidence of ovarian cancer in the over-65 population. CONCLUSION: The budget impact of adding rucaparib to the formulary for a health plan adds negligible PMPM costs of < US$0.001 in all tested settings and scenarios due to the small population eligible for therapy.

Watchful waiting and health related quality of life for patients with localized prostate cancer: data from CaPSURE.

PURPOSE: Watchful waiting is an alternative to active treatment for men with low risk prostate cancer but it is unclear how health related quality of life (HRQoL) may change over time for men who select this option. We report on HRQoL in men with localized prostate cancer who selected watchful waiting. MATERIALS AND METHODS: HRQoL outcomes were reviewed for 310 men diagnosed with prostate cancer from 1990 to 2001 within Cancer of the Prostate Strategic Urological Research Endeavor who chose watchful waiting. The UCLA Prostate Cancer Index and RAND 36-Item Health Survey were completed at enrollment and approximately every 6 months. A random slopes model was developed to assess time trends in HRQoL for up to 5 years after diagnosis, adjusting for age at diagnosis and specific comorbidities. RESULTS: Significant decreases with time were observed in 7 domains of the RAND 36-Item Health Survey and 4 of the UCLA Prostate Cancer Index scales. CONCLUSIONS: Men with prostate cancer who chose watchful waiting in the current study had better or similar HRQoL outcomes compared to men without prostate cancer at the start of the study. Many of these scores were significantly affected by increasing age and decreased with time. The physical domain scores as well as sexual function scores decreased more than expected from the aging process alone.

Clinical and psychosocial characteristics of men with erectile dysfunction: baseline data from ExCEED.

INTRODUCTION: Erectile dysfunction (ED) is associated with psychological impairment, and further research is required to understand their relationship. AIM: We present descriptive baseline results from a longitudinal observational study of North American men seeking treatment for ED. METHODS: Patients completed clinical and health-related quality-of-life information at baseline and three follow-up points over 12 months; 162 patients had usable baseline data, including clinical history and current status, sociodemographic information, and standard paper-and-pencil scales of psychosocial characteristics. Scores on the International Index of Erectile Functioning erectile functioning subscale were collapsed into mild (N = 27), moderate (N = 41), or severe (N = 94) categories. Using chi-square, anova, and logistic regression, we identified baseline characteristics associated with ED severity. MAIN OUTCOME MEASURE: The main outcome measure was the degree of psychosocial impairment associated with mild, moderate, and severe ED. RESULTS: Severe ED was significantly associated with not having a regular sex partner; a history of prostate cancer; and worse scores on measures of positive affect, belonging/loneliness, sexual self-efficacy-strength, psychological adjustment, marital happiness, anxiety at last intercourse, and depression. In a multivariate logistic regression model, poorer sexual self-efficacy was most closely associated with severe ED. The model rescaled R(2) was 0.63 (area-under-the-curve, 0.91). CONCLUSIONS: Severe ED is related to impairment across a broad range of psychosocial domains, and clinicians should consider offering patients assistance in dealing with its psychosocial impact.

Obesity and prostate cancer clinical risk factors at presentation: data from CaPSURE.

PURPOSE: We investigated the association of obesity with prostate cancer case demographics and clinical disease features at presentation. MATERIALS AND METHODS: Data were abstracted from CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor), a disease registry of 10,018 men with prostate cancer. A total of 2,952 men were included who were treated between 1989 and 2002, and had complete body mass index (BMI) information. BMI classes were defined as normal (less than 25 kg/m), overweight (25 to 29.9 kg/m), obese (30 to 34.9 kg/m) or very obese (35 kg/m or greater). Patients were categorized as having low, intermediate or high risk disease based on the D'Amico classification. Associations among BMI, risk and demographics were analyzed using univariate and multivariate models. RESULTS: Of the patients 29% had a normal BMI, 51% were overweight, 16% were obese and 5% were very obese. Patients who were overweight or obese were more likely to be young, have hypertension and diabetes, and have a lower education level. The overweight group had a lower serum prostate specific antigen (p = 0.010) and lower stage disease (p = 0.030) at diagnosis, but there was no association between Gleason score and obesity (p = 0.57). However, among men with a BMI of 25 kg/m or greater there was a positive correlation between increasing BMI and risk of being in a worse prognostic group at diagnosis (p = 0.018). CONCLUSIONS: Overweight and obese patients are more likely to be young at diagnosis and have multiple comorbidities. Men in the overweight and obese groups presented with lower risk prostate cancer at diagnosis. This may be due to earlier disease detection secondary to more frequent interaction with the medical community. Among overweight and obese patients increased obesity is associated with a slightly increased chance of having high risk prostate cancer at diagnosis.

Watchful waiting and health related quality of life for patients with localized prostate cancer: data from CaPSURE.

PURPOSE: Watchful waiting is an alternative to active treatment for men with low risk prostate cancer but it is unclear how health related quality of life (HRQoL) may change over time for men who select this option. We report on HRQoL in men with localized prostate cancer who selected watchful waiting. MATERIALS AND METHODS: HRQoL outcomes were reviewed for 310 men diagnosed with prostate cancer from 1990 to 2001 within Cancer of the Prostate Strategic Urological Research Endeavor who chose watchful waiting. The UCLA Prostate Cancer Index and RAND 36-Item Health Survey were completed at enrollment and approximately every 6 months. A random slopes model was developed to assess time trends in HRQoL for up to 5 years after diagnosis, adjusting for age at diagnosis and specific comorbidities. RESULTS: Significant decreases with time were observed in 7 domains of the RAND 36-Item Health Survey and 4 of the UCLA Prostate Cancer Index scales. CONCLUSIONS: Men with prostate cancer who chose watchful waiting in the current study had better or similar HRQoL outcomes compared to men without prostate cancer at the start of the study. Many of these scores were significantly affected by increasing age and decreased with time. The physical domain scores as well as sexual function scores decreased more than expected from the aging process alone.

Compliance with allopurinol therapy among managed care enrollees with gout: a retrospective analysis of administrative claims.

OBJECTIVE: Poor compliance with gout medications has been recognized, but seldom studied. We investigated compliance with allopurinol among managed care enrollees suspected to have gout. METHODS: This was a retrospective, administrative claims-based analysis of patients with gout. Compliance with allopurinol was measured using prescription-fill dates and days-supplied amounts. Compliance was defined for each prescription period as the presumed use of allopurinol on at least 80% of the days of that period. RESULTS: Of 9482 patients identified, 65.9% filled at least one prescription for allopurinol during the 24 month followup period; 10.4% of allopurinol users filled one prescription and then discontinued use. Of the remaining patients, 13.7% never achieved compliance with therapy; 18% were compliant throughout the entire followup period. Patients were compliant with therapy for an average of 56% of their treatment periods and noncompliant for an average of 44%. In multivariate analysis, male sex was associated with decreased compliance (p < 0.01), although the effect was mitigated by increasing age. For subjects of both sexes, increasing age was associated with increased compliance (p < 0.05). CONCLUSION: Compliance with allopurinol in this population was low. Because untreated gouty arthritis can lead to serious adverse outcomes (such as recurrent gouty arthritis, chronic gouty arthropathy, tophi, and urolithiasis) that are usually avoidable with antihyperuricemic therapy, efforts to achieve better compliance are warranted.

Patterns of practice in the United States: insights from CaPSURE on prostate cancer management.

The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) is a national disease registry of more than 10,000 patients with prostate cancer treated at 31 primarily community-based sites across the country. The database tracks oncologic and health-related quality-of-life outcomes. Because the urologists participating in the project treat according to their usual practices, CaPSURE facilitates the study of trends in disease-management strategies, offering a reflection of "real world" practice patterns. This review highlights key studies during the past several years that document downward risk migration, validates widely used prognostic nomograms, establishes prostate-specific antigen doubling time as a surrogate endpoint for disease-specific mortality, assesses the impact of treatment on patient-reported quality of life, and presents national trends in imaging test use and primary treatment strategies for localized disease.

Validation of the Kattan preoperative nomogram for prostate cancer recurrence using a community based cohort: results from cancer of the prostate strategic urological research endeavor (capsure).

PURPOSE: The Kattan preoperative nomogram combines preoperative prostate specific antigen (PSA), biopsy Gleason grade and clinical stage to estimate disease recurrence after radical prostatectomy. Several studies using patient data from academic centers have validated the nomogram. We assessed the performance of the Kattan nomogram using the Cancer of the Prostate Strategic Urological Research Endeavor database, a national, largely community based observational disease registry. MATERIALS AND METHODS: From the Cancer of the Prostate Strategic Urological Research Endeavor database we identified 1701 men with clinically localized prostate cancer undergoing radical prostatectomy with sufficient pretreatment information and PSA followup after surgery. Disease recurrence was defined as 2 consecutive PSA values 0.2 ng/ml or greater, or a second cancer treatment more than 6 months after prostatectomy. A concordance index was used to evaluate the performance of the nomogram compared to observed 5-year recurrence-free survival (Kaplan-Meier). Kattan nomogram scores were calculated for each patient and stratified into 6 groups for analysis. RESULTS: In our cohort of 1701 men 413 (24%) had evidence of disease recurrence. Median followup in these patients was 2.3 years. Kattan nomogram scores were 17% to 99% (mean 79%). The overall concordance index was 0.68. Varying the definition of recurrent disease and excluding patients with imputed data did not substantially alter nomogram performance (concordance index 0.65 to 0.70). The Kattan nomogram tended to overestimate 5-year freedom from recurrence in patients with scores of 65% and higher. CONCLUSIONS: We noted the reasonable performance of the Kattan nomogram for predicting cancer outcomes after radical prostatectomy using a community based population. Although concordance is lower than in previous validation studies and the nomogram overestimates recurrence-free survival in patients at lower risk, the model is fairly robust and it provides important information when counseling patients regarding treatment options in the community setting. Further refinements in pretreatment estimation of disease-free survival and ultimately overall survival are needed.

Is quality of life different for men with erectile dysfunction and prostate cancer compared to men with erectile dysfunction due to other causes? Results from the ExCEED data base.

PURPOSE: To our knowledge the relationship between the underlying etiology of erectile dysfunction and its impact on health related quality of life has not been studied. Such a study is important for men with prostate cancer, as the potential negative quality of life impact of erectile dysfunction may affect clinical decision making in newly diagnosed disease. We compare health related quality of life in impotent men with prostate cancer to that of impotent men without prostate cancer using the Exploratory and Comprehensive Evaluation of Erectile Dysfunction (ExCEED, TAP Pharmaceutical Products, Inc., Lake Forest, Illinois) data base, which is a multicenter, observational disease registry of men with erectile dysfunction. MATERIALS AND METHODS: The cohort included 168 men in ExCEED who had baseline health related quality of life measurement. Of these men 47 reported a history of prostate cancer while 121 did not. Appropriate univariate and multivariate analyses were performed comparing health related quality of life outcomes between impotent men with and without prostate cancer. RESULTS: Men with erectile dysfunction and prostate cancer had worse sexual self-efficacy, erectile function, intercourse satisfaction and orgasmic function than those with erectile dysfunction without prostate cancer (all p <0.001). However, men with erectile dysfunction and prostate cancer experienced less psychological impact of erectile dysfunction on sexual experience (p = 0.05) and emotional life (p = 0.03) than those with erectile dysfunction without prostate cancer. The findings regarding the psychological impact of erectile dysfunction persisted in multivariate linear regression models. CONCLUSIONS: Men with erectile dysfunction and prostate cancer appear to have better disease specific health related quality of life than those with erectile dysfunction and no history of prostate cancer. This finding has important ramifications for clinicians when counseling patients newly diagnosed with prostate cancer and also when treating patients who present with erectile dysfunction of various etiologies.