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Brief Report
September 26, 2019

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

Author Affiliations
  • 1Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona
  • 2Department of Medicine, Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
  • 3Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
  • 4Division of Hematology, Mayo Clinic, Rochester, Minnesota
  • 5Exelixis Inc, South San Francisco, California
  • 6Independent Consultant, San Francisco, California
  • 7Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
JAMA Oncol. 2020;6(2):e193332. doi:10.1001/jamaoncol.2019.3332
Key Points

Question  Is implementation of the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) feasible in a phase 3 cancer trial, and how well can PRO-CTCAE be used to detect between-group differences in symptomatic adverse events relative to the Common Terminology Criteria for Adverse Events?

Findings  In this prespecified correlative analysis of the randomized COMET-2 trial of 119 patients with prostate cancer in which patients completed the PRO-CTCAE at baseline and every 3 weeks during treatment, 534 of 587 (91.0%) expected PRO-CTCAE self-reports were completed. The rates of 7 symptomatic adverse events were statistically significantly different between groups by PRO-CTCAE, while none were statistically significantly different by the Common Terminology Criteria for Adverse Events.

Meaning  PRO-CTCAE data collection was feasible and improved the accuracy of symptomatic adverse event detection in this phase 3 cancer 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 < .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.

Trial Registration  ClinicalTrials.gov identifier: NCT01522443

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