Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Age Ageing. 2018 Sep 1;47(5):654-660. doi: 10.1093/ageing/afy079.
older patients are commonly believed to derive less benefit from cancer drugs, even if they fulfil clinical trial eligibility [Talarico et al. (2004, J Clin Oncol, 22(22):4626-31)]. We aim to examine if novel oncology drugs provide differential age-based treatment outcomes for patients on clinical trials.
a systematic review of randomised control trials (RCTs) cited for clinical efficacy evidence in novel oncology drug approvals by the Food and Drug Administration, European Medicines Agency and Health Canada between 2006 and 2017 was conducted. Studies reporting age-based subgroup analyses for overall or progression-free survival (OS/PFS) were included. Hazard ratios (HRs) and confidence intervals (CIs) for age-based subgroups were extracted. Meta-analyses with random effects were conducted, examining patient subgroups <65 and ≥65 years separately and pooled HRs of studies primary endpoints (OS or PFS) compared to examine if differences existed between age-based subgroups. Sensitivity analyses were conducted for cancer type, primary endpoint and systemic treatment.
one-hundred-two RCTs, including 65,122 patients, met the inclusion criteria. One study reported age-based toxicity and none reported age-based quality of life (QOL) results. Pooled HRs [95% CIs] for patients <65 and ≥65 years were 0.61 [0.57-0.65] and 0.65 [0.61-0.70], respectively, with no difference between them (P = 0.14). Sensitivity analyses revealed similar results.
our results suggest that older and young patients, who fulfil clinical trial eligibility, may derive similar relative survival benefits from novel oncology drugs. There is, however, a need to report age-based toxicity and QOL results to support patient discussions regarding the balance of treatment benefit and harm, to encourage informed decision-making.
即使符合临床试验的纳入标准，老年人通常也被认为从癌症药物中获益较少[Talarico 等人（2004 年，J Clin Oncol，22（22）：4626-31）]。我们旨在研究新型肿瘤药物是否为临床试验患者提供了基于年龄的不同治疗效果。
对 2006 年至 2017 年间，美国食品和药物管理局、欧洲药品管理局和加拿大卫生部批准新型肿瘤药物的临床疗效证据中引用的随机对照试验（RCT）进行了系统回顾。纳入了报告总生存（OS）/无进展生存（PFS）基于年龄亚组分析的研究。提取了基于年龄亚组的风险比（HR）和置信区间（CI）。分别对<65 岁和≥65 岁的患者亚组进行了荟萃分析，比较了研究主要终点（OS 或 PFS）的合并 HR，以研究年龄亚组之间是否存在差异。还对癌症类型、主要终点和系统治疗进行了敏感性分析。
符合纳入标准的有 102 项 RCT，共纳入 65122 例患者。有一项研究报告了基于年龄的毒性，没有研究报告了基于年龄的生活质量（QOL）结果。<65 岁和≥65 岁患者的合并 HR（95%CI）分别为 0.61（0.57-0.65）和 0.65（0.61-0.70），两者之间无差异（P=0.14）。敏感性分析显示了类似的结果。
我们的研究结果表明，符合临床试验纳入标准的老年和年轻患者可能从新型肿瘤药物中获得相似的相对生存获益。然而，有必要报告基于年龄的毒性和 QOL 结果，以支持患者关于治疗获益和危害平衡的讨论，鼓励知情决策。
