TY - JOUR
T1 - Assessment of Adverse Events from the Patient Perspective in a Phase 3 Metastatic Castration-Resistant Prostate Cancer Clinical Trial
AU - Dueck, Amylou C.
AU - Scher, Howard I.
AU - Bennett, Antonia V.
AU - Mazza, Gina L.
AU - Thanarajasingam, Gita
AU - Schwab, Gisela
AU - Weitzman, Aaron L.
AU - Rogak, Lauren J.
AU - Basch, Ethan
N1 - Funding Information:
Accepted for Publication: June 15, 2019. Published Online: September 26, 2019. doi:10.1001/jamaoncol.2019.3332 AuthorContributions:DrDueckhadfullaccesstoallthe datainthestudyandtakesresponsibilityfortheintegrity of the data and the accuracy of the data analysis. Concept and design: Dueck, Scher, Bennett, Schwab, Weitzman, Basch. Acquisition, analysis, or interpretation of data: Dueck, Mazza, Thanarajasingam, Schwab, Rogak, Basch. Drafting of the manuscript: Dueck, Thanarajasingam, Rogak, Basch. Critical revision of the manuscript for important intellectual content: Dueck, Scher, Bennett, Mazza, Thanarajasingam, Schwab, Weitzman, Basch. Statistical analysis: Dueck, Mazza, Thanarajasingam. Obtained funding: Scher. Administrative, technical, or material support: Scher, Schwab, Rogak. Supervision: Scher, Schwab, Basch. Conflict of Interest Disclosures: Dr Dueck reported receivinggrantsfromtheNationalCancerInstituteduring the conduct of the study. Dr Scher reported receiving personal fees and nonfinancial support from Asterias Biotherapeutics,AmbryGeneticsCorp,KonicaMinolta Inc, and WCG Oncology; nonfinancial support from Amgen, ESSA Pharma Inc, Janssen R & D, Janssen Biotech Inc, Menarini Silicon, Sanofi, and Clovis Oncology; and grants from Epic Sciences, Illumina Inc, InnocrinPharma,Janssen,MenariniSilicon,andThermo Fisher outside the submitted work. Dr Mazza reported receiving grants from the National Cancer Institute during the conduct of the study. Dr Thanarajasingam reportedreceivinggrantsfromtheNationalInstitutesof Health during the conduct of the study. Dr Schwab reportedbeinganemployeeandshareholderofExelixis Inc, the company that sponsored the clinical trial providing data for this publication. Dr Basch reported receivinggrantsfromtheNationalCancerInstituteand the Patient-Centered Outcomes Research Institute; editorial support from JAMA; research consultant fees fromDana-FarberCancerInstituteandMemorialSloan Kettering Cancer Center; primary employment from University of North Carolina; and personal fees from Sivan, CareVive, and Self Care Catalyst outside the submitted work. No other disclosures were reported. Funding/Support: Funding for this analysis was providedthroughtheCancerMoonshotinitiativeofthe US National Cancer Institute (grant U01 CA233046). Role of the Funder/Sponsor: The funding source had noroleinthedesignandconductofthestudy;collection, management, analysis, and interpretation of the data; preparation,review,orapprovalofthemanuscript;and decision to submit the manuscript for publication. AdditionalInformation:DatawereprovidedbyExelixis Incforthistrial,butExelixisIncdidnotprovideanyfunds and did not participate in the decision to submit this manuscript, analysis, or approval of the submission.
PY - 2020/2
Y1 - 2020/2
N2 - 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 <.05), and use of a method for accounting for preexisting symptoms at baseline yielded 7 AEs with statistically significant differences between groups (differences ranged from 20.5% to 41.2% with higher proportions in the cabozantinib group; all P <.05). In the same analysis using investigator-reported CTCAE data, no statistically significant differences were found between groups for any symptomatic AEs. Conclusions and Relevance: PRO-CTCAE data collection was feasible and improved the accuracy of symptomatic AE detection in a phase 3 cancer trial. This analysis adds to mounting evidence of the feasibility and value of patient-reported AEs in oncology, which should be considered for inclusion in cancer trials that incorporate AE evaluation.
AB - 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 <.05), and use of a method for accounting for preexisting symptoms at baseline yielded 7 AEs with statistically significant differences between groups (differences ranged from 20.5% to 41.2% with higher proportions in the cabozantinib group; all P <.05). In the same analysis using investigator-reported CTCAE data, no statistically significant differences were found between groups for any symptomatic AEs. Conclusions and Relevance: PRO-CTCAE data collection was feasible and improved the accuracy of symptomatic AE detection in a phase 3 cancer trial. This analysis adds to mounting evidence of the feasibility and value of patient-reported AEs in oncology, which should be considered for inclusion in cancer trials that incorporate AE evaluation.
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U2 - 10.1001/jamaoncol.2019.3332
DO - 10.1001/jamaoncol.2019.3332
M3 - Article
C2 - 31556911
AN - SCOPUS:85072751140
VL - 6
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
IS - 2
M1 - e193332
ER -