Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Harvard Medical School, Boston, MA.
Int J Cancer. 2019 Apr 1;144(7):1746-1751. doi: 10.1002/ijc.31957. Epub 2018 Dec 6.
Quality of life outcomes provide essential information for patients and physicians in oncology care. However, the validity of progression-free survival (PFS) as a surrogate for quality of life, and the inclusion and reporting of quality of life endpoints in clinical trials, is unclear. We performed a retrospective study of phase III clinical trials of drugs for advanced or metastatic solid tumors published between 2010 and 2015. Correlation coefficient (r) and area under the ROC curve (AUC) for association between PFS and positive quality of life were evaluated. Of the 352 Phase 3 trials included, 190 (54%) included a quality of life endpoint, of which 23% did not report pre-specified quality of life outcomes; a total of 125,962 patients were enrolled in studies lacking, or not reporting, quality of life outcomes. Among the 147 trials that reported quality of life outcomes, 99 (67%) reported no effect, 38 (26%) reported a positive effect and 10 (7%) reported a negative effect of treatment on patients' global quality of life. The association between PFS and improvement in global quality of life was weak (r = 0.34; AUC = 0.72), as was the association between PFS and improvement in any domain of quality of life. In conclusion, PFS benefit was not strongly correlated with improvements in patients' quality of life, and, despite the palliative intent of treatments in the advanced/metastatic setting, the availability of quality of life data from clinical trials of cancer drugs was poor.
生活质量结果为肿瘤学治疗中的患者和医生提供了重要信息。然而,无进展生存期(PFS)作为生活质量替代指标的有效性,以及临床试验中生活质量终点的纳入和报告尚不清楚。我们对 2010 年至 2015 年期间发表的用于治疗晚期或转移性实体瘤的 III 期药物临床试验进行了回顾性研究。评估了 PFS 与阳性生活质量之间的相关性系数(r)和 ROC 曲线下面积(AUC)。在纳入的 352 项 III 期试验中,有 190 项(54%)包含生活质量终点,其中 23%未报告预先指定的生活质量结果;共有 125962 名患者入组了未报告或未报告生活质量结果的研究。在报告生活质量结果的 147 项试验中,99 项(67%)报告无效果,38 项(26%)报告治疗对患者整体生活质量有积极影响,10 项(7%)报告治疗对患者整体生活质量有消极影响。PFS 与整体生活质量改善之间的相关性较弱(r=0.34;AUC=0.72),PFS 与生活质量任何领域改善之间的相关性也较弱。总之,PFS 获益与患者生活质量的改善没有很强的相关性,而且,尽管在晚期/转移性环境中治疗具有姑息性意图,但癌症药物临床试验中生活质量数据的可用性较差。
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