Schapira Marilyn M, Stevens Evelyn M, Sharpe James E, Hochman Lauren, Reiter Joseph G, Calhoun Shawna R, Shah Shivani A, Bailey Leonard Charles, Bagatell Rochelle, Silber Jeffrey H, Tai Eric, Barakat Lamia P
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Center for Health Equity Research and Promotion (CHERP), Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA.
Cancer. 2020 Aug 1;126(15):3471-3482. doi: 10.1002/cncr.32947. Epub 2020 May 26.
Approximately 50% of children with cancer in the United States who are aged <15 years receive primary treatment on a therapeutic clinical trial. To the authors' knowledge, it remains unknown whether trial enrollment has a clinical benefit compared with the best alternative standard therapy and/or off trial (ie, clinical trial effect). The authors conducted a retrospective matched cohort study to compare the morbidity and mortality of pediatric patients with cancer who are treated on a phase 3 clinical trial compared with those receiving standard therapy and/or off trial.
Subjects were aged birth to 19 years; were diagnosed between 2000 and 2010 with acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), rhabdomyosarcoma, or neuroblastoma; and had received initial treatment at the Children's Hospital of Philadelphia. On-trial and off-trial subjects were matched based on age, race, ethnicity, a diagnosis of Down syndrome (for patients with ALL or AML), prognostic risk level, date of diagnosis, and tumor type.
A total of 428 participants were matched in 214 pairs (152 pairs for ALL, 24 pairs for AML, 32 pairs for rhabdomyosarcoma, and 6 pairs for neuroblastoma). The 5-year survival rate did not differ between those treated on trial versus those treated with standard therapy and/or off trial (86.9% vs 82.2%; P = .093). On-trial patients had a 32% lower odds of having worse (higher) mortality-morbidity composite scores, although this did not reach statistical significance (odds ratio, 0.68; 95% confidence interval, 0.45-1.03 [P = .070]).
There was no statistically significant difference in outcomes noted between those patients treated on trial and those treated with standard therapy and/or off trial. However, in partial support of the clinical trial effect, the results of the current study indicate a trend toward more favorable outcomes in children treated on trial compared with those treated with standard therapy and/or off trial. These findings can support decision making regarding enrollment in pediatric phase 3 clinical trials.
在美国，年龄小于15岁的癌症患儿中约有50%在治疗性临床试验中接受初始治疗。据作者所知，与最佳替代标准疗法和/或非试验治疗（即临床试验效应）相比，参与试验是否具有临床益处仍不清楚。作者进行了一项回顾性匹配队列研究，以比较在3期临床试验中接受治疗的儿科癌症患者与接受标准疗法和/或非试验治疗的患者的发病率和死亡率。
研究对象年龄为出生至19岁；在2000年至2010年期间被诊断为急性淋巴细胞白血病（ALL）、急性髓细胞白血病（AML）、横纹肌肉瘤或神经母细胞瘤；并在费城儿童医院接受了初始治疗。试验组和非试验组受试者根据年龄、种族、民族、唐氏综合征诊断（针对ALL或AML患者）、预后风险水平、诊断日期和肿瘤类型进行匹配。
总共428名参与者被匹配成214对（ALL为152对，AML为24对，横纹肌肉瘤为32对，神经母细胞瘤为6对）。试验组治疗患者与接受标准疗法和/或非试验治疗患者的5年生存率无差异（86.9%对82.2%；P = 0.093）。试验组患者出现更差（更高）死亡率 - 发病率综合评分的几率低32%，尽管这未达到统计学显著性（优势比，0.68；95%置信区间，0.45 - 1.03 [P = 0.070]）。
在试验组治疗患者与接受标准疗法和/或非试验治疗患者之间，观察到的结局无统计学显著差异。然而，为临床试验效应提供部分支持的是，本研究结果表明，与接受标准疗法和/或非试验治疗的儿童相比，试验组治疗的儿童有出现更有利结局的趋势。这些发现可为儿科3期临床试验的入组决策提供支持。
