Performance Status Restriction in Phase III Cancer Clinical Trials
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German Cancer Research Center, Heidelberg, Germany;
German Cancer Consortium, Frankfurt, Germany;
Frankfurt Cancer Institute, Frankfurt, Germany;
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German Cancer Research Center, Heidelberg, Germany;
German Cancer Consortium, Frankfurt, Germany;
Frankfurt Cancer Institute, Frankfurt, Germany;
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Background: Patients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We aimed to characterize trial-related factors associated with the use of PS eligibility criteria and analyze patient accrual breakdown by PS. Methods: Adult, therapeutic, multiarm phase III cancer-specific RCTs were identified through ClinicalTrials.gov. PS data were extracted from articles. Trials with a PS restriction ECOG score ≤1 were identified. Factors associated with PS restriction were determined, and the use of PS restrictions was analyzed over time. Results: In total, 600 trials were included and 238,213 patients had PS data. Of those trials, 527 studies (87.8%) specified a PS restriction cutoff, with 237 (39.5%) having a strict inclusion criterion (ECOG PS ≤1). Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (P<.001) and lung cancer trials (P<.001). Nearly half of trials that led to FDA approval included strict PS restrictions. Most patients enrolled across all trials had an ECOG PS of 0 to 1 (96.3%). Even among trials that allowed patients with ECOG PS ≥2, only 8.1% of those enrolled had a poor PS. Trials of lung, breast, gastrointestinal, and genitourinary cancers all included <5% of patients with poor PS. Finally, only 4.7% of patients enrolled in trials that led to subsequent FDA approval had poor PS. Conclusions: Use of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring to ensure the generalizability of results while maintaining patient safety.
Submitted March 7, 2020; accepted for publication April 16, 2020.
Author contributions: Study concept and design: Jaoude, Kouzy, Taniguchi, Ludmir. Data collection: Jaoude, Kouzy, Mainwaring, Lin, Miller, Jethanandani, Espinoza, Ludmir. Data analysis and interpretation: All authors. Manuscript preparation: All authors.
Disclosures: Dr. VanderWalde has disclosed that he receives consulting fees from Vector Oncology. Dr. B.D. Smith has disclosed that he has received grant/research support from Varian Medical Systems, and has an equity interest in Oncora Medical. Dr. Fuller has disclosed that he receives royalty income from Demos Medical Publishing, and honoraria from Elekta AB. Dr. Das has disclosed that he receives consulting fees from Adlai Nortye. Dr. Jagsi has disclosed that she has is a scientific advisor for Equity Quotient, has received honoraria from Amgen and Vizient, and has received grant/research support from the Doris Duke Foundation, the Greenwall Foundation, the Komen Foundation, and Blue Cross Blue Shield of Michigan. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: Dr. Taniguchi is supported by funding from NIH (award R01CA227517-01A1), Cancer Prevention & Research Institute of Texas (CPRIT; grant RR140012), V Foundation (V2015-22), the Kimmel Foundation, Sabin Family Foundation Fellowship, and the McNair Foundation. This manuscript is also supported by NIH P30 CA016672.
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