Dataset Information

Assessment of Adverse Events From the Patient Perspective in a Phase 3 Metastatic Castration-Resistant Prostate Cancer Clinical Trial.

ABSTRACT: Importance:Standard adverse event (AE) reporting in oncology clinical trials has historically relied on clinician grading, which prior research has shown can lead to underestimation of rates of symptomatic AEs. Industry sponsors are beginning to implement in trials the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), which was developed to allow patients to self-report symptomatic AEs and improve the quality of symptomatic AE detection. Objectives:To evaluate the feasibility of implementing PRO-CTCAE in a prespecified correlative analysis of the phase 3 COMET-2 trial and enumerate statistically significant between-group differences in symptomatic AEs using PRO-CTCAE and the CTCAE. Design, Setting, and Participants:This correlative study of 119 men in the randomized, double-blind, placebo-controlled phase 3 COMET-2 trial with metastatic castration-resistant prostate cancer who had undergone at least 2 prior lines of systemic treatment was conducted from March 2012 to July 2014. Participants completed PRO-CTCAE items using an automated telephone system from home prior to treatment and every 3 weeks during treatment. Statistical analysis was performed from May 2018 to June 2019. Main Outcomes and Measures:The proportion of patients who completed expected PRO-CTCAE self-reports was computed as a measure of feasibility. Results:Among the 119 men in the study (median age, 65 years [range, 44-80 years]), 534 of 587 (91.0%) expected PRO-CTCAE self-reports were completed, with consistently high rates of completion throughout participation. Rates of self-report adherence were similar between groups (cabozantinib s-maleate, 286 of 317 [90.2%]; and mitoxantrone hydrochloride-prednisone, 248 of 270 [91.9%]). Of 12 measured, patient-reported PRO-CTCAE symptomatic AEs, 4 reached statistical significance when comparing the proportion of patients with at least 1 postbaseline score greater than 0 between groups (differences ranged from 20.1% to 34.1% with higher proportions in the cabozantinib group; all P?

SUBMITTER: Dueck AC

PROVIDER: S-EPMC6764147 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Assessment of Adverse Events From the Patient Perspective in a Phase 3 Metastatic Castration-Resistant Prostate Cancer Clinical Trial.

Dueck Amylou C AC Scher Howard I HI Bennett Antonia V AV Mazza Gina L GL Thanarajasingam Gita G Schwab Gisela G Weitzman Aaron L AL Rogak Lauren J LJ Basch Ethan E

JAMA oncology 20200213 2

<h4>Importance</h4>Standard adverse event (AE) reporting in oncology clinical trials has historically relied on clinician grading, which prior research has shown can lead to underestimation of rates of symptomatic AEs. Industry sponsors are beginning to implement in trials the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), which was developed to allow patients to self-report symptomatic AEs and improve the quality ...[more]

PMID: 31556911

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Project description:ObjectivesWith novel antiandrogen treatments of varying clinical benefits and risks becoming available, this study investigates how patients with castration-resistant prostate cancer (CRPC) value differences in treatment characteristics.DesignCross-sectional observational study.SettingA discrete choice experiment was conducted. Patients chose between two hypothetical non-metastatic CRPC (nmCRPC) treatments defined by six attributes: risk of fatigue, falls or fracture, cognitive impairment, hypertension, rashes as side effects to treatment and extension of time until cancer-related pain occurs.ParticipantsA total of 137 adult male patients with CRPC with no prior experience with chemotherapy and with Eastern Cooperative Oncology Group status 0-1 were recruited. Patients were excluded if they participated in an investigational programme outside of routine clinical practice, had a clinically relevant medical or psychiatric condition, or diagnosis of visceral/other metastases not related to the prostate, or were otherwise deemed ineligible by the referring physician.Primary outcome measuresRelative preference weights and relative importance of the attributes was estimated by hierarchical Bayesian logistic regression.ResultsAmong the treatment attributes, 'risk of cognitive impairment as a side effect of treatment' was the most important attribute (relative importance (RI) (95% CI): 27.47% (24.80% to 30.14%)), followed by 'extension of time until cancer-related pain occurs' (RI (95% CI): 17.87% (15.49% to 20.25%)) and the 'risk of falls or fracture' (RI (95% CI): 15.99% (14.73% to 17.25%)). The 'risk of hypertension as a side effect of treatment' (RI (95% CI): 13.77% (12.73% to 14.81%)) had similar RI as 'risk of rashes as a side effect of treatment' (RI (95% CI): 13.17% (12.15% to 14.19%)), followed by the 'risk of fatigue as a side effect of treatment' (RI (95% CI): 11.74% (10.75% to 12.73%)).ConclusionsPatients consider the risk of cognitive impairment as a side effect of treatment as the most important attribute in nmCRPC, followed by the extension of time until cancer-related pain occurs, and the risk of falls and fracture. These features should be considered in treatment decision making for nmCRPC in Japan.

Project description:IntroductionThree novel androgen receptor inhibitors are approved in the USA for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC): apalutamide, enzalutamide, and darolutamide. All three therapies have demonstrated prolonged metastasis-free survival in their respective phase III trials, with differing safety profiles. The objective of this study was to compare the mean per-patient costs of all-cause adverse events (AEs) requiring hospitalization between darolutamide versus apalutamide and enzalutamide for nmCRPC in the USA.MethodsAll-cause grade ≥ 3 AEs with corresponding any-grade AEs reported among at least 10% of patients in any arm of the ARAMIS (darolutamide), SPARTAN (apalutamide), and PROSPER (enzalutamide) trials were selected for inclusion in the primary analyses. After matching-adjusted indirect comparison, AE costs were calculated by multiplying the AE rates from the trials by their respective unit costs of hospitalization taken from the US Healthcare Cost and Utilization Project (HCUP) database. Sensitivity analyses which further included any-grade AEs reported among at least 5% of patients were also performed.ResultsAfter reweighting and adjusting for the trials' placebo arms, the mean per-patient AE costs were $1021 and $387 lower for darolutamide than for apalutamide and enzalutamide, respectively, over the trials' duration (SPARTAN and PROSPER, 43 months; ARAMIS, 48 months). For darolutamide vs. apalutamide, the largest drivers of the per-patient cost differences were fracture (adjusted difference $416), hypertension ($143), and rash ($219); for darolutamide vs. enzalutamide, they were fatigue not including asthenia ($290) and hypertension including increased blood pressure (i.e., any AE of hypertension or with elevated blood pressure not yet classified as hypertension) ($60). The results of the sensitivity analyses were consistent with the primary results.ConclusionsPatients with nmCRPC treated with darolutamide in ARAMIS incurred lower AE-related costs (USD), as determined using HCUP costing data, compared with patients treated with either apalutamide (in SPARTAN) or enzalutamide (in PROSPER).

Project description:ObjectiveThe study objectives were to understand how patients view the quality of life in non-metastatic castration-resistant prostate cancer (nmCRPC), including unmet needs and what patients consider most important in treatment outcomes. A gap analysis was conducted on existing patient-reported outcomes (PROs) measures versus what is missing from the patient perspective, to guide future development of PRO-based real-world evidence for nmCRPC in Japan. A conceptual model for nmCRPC Japanese patients' HRQOL was also created.MethodsThis non-interventional, qualitative study consisted of a targeted literature review, PRO instrument review, and interviews with 20 nmCRPC patients and five treating physicians. Triangulation of the gap analysis, evidence from the targeted review of the literature, and qualitative interview findings were employed to assess the comprehensiveness of current nmCRPC and HRQOL measures.ResultsSymptoms most reported by patients were frequent urination (70%), nocturia (65%), and general pain (65%). Others reported included lack of strength (30%). HRQOL impacts most reported were anxiety (45%) and worry (50%) about their diagnosis. Additional impacts mentioned were weight changes, loss of sleep, difficulty walking, loss of appetite, and difficulty traveling and seeking toilets in public. The gap analysis revealed 31 symptoms and 33 impacts not covered in existing prostate cancer-specific PRO instruments. Patients mentioned musculoskeletal symptoms such as fractures, leg pain, cramps, numbness, and loss of leg bone strength. Impacts not previously discussed in the literature or in outcome measures were feelings of self-consciousness around diagnosis, stigma around illness, and the impact on mobility including traveling.ConclusionKey results reveal pain and urinary symptoms are the most experienced by Japanese nmCRPC patients. The diagnosis and treatment of disease leads to significant impacts in patient lives. Analysis revealed that symptoms and life impacts are missing in the current literature and outcome measures. Testing and debriefing of specific items could further substantiate these dimensions.

Dataset Information

Assessment of Adverse Events From the Patient Perspective in a Phase 3 Metastatic Castration-Resistant Prostate Cancer Clinical Trial.

Publications

Assessment of Adverse Events From the Patient Perspective in a Phase 3 Metastatic Castration-Resistant Prostate Cancer Clinical Trial.

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