Prawira A, Oosting S F, Chen T W, Delos Santos K A, Saluja R, Wang L, Siu L L, Chan K K W, Hansen A R
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
Br J Cancer. 2017 Dec 5;117(12):1743-1752. doi: 10.1038/bjc.2017.357. Epub 2017 Oct 24.
The majority of published studies in recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are single-arm trials. Reliable modelling of progression-free survival (PFS) and overall survival (OS) outcomes, therefore, is difficult. This study aim to analyse existent literature to estimate the relative efficacy of available systemic regimens in RM-NPC, as well as provide estimates of aggregate OS and PFS.
We conducted a systematic search of MEDLINE, EMBASE and the Cochrane Library to March 2015. Clinical trials (in English only) investigating cytotoxic and molecularly targeted agents in adult patients with RM-NPC were included. All relevant studies were assessed for quality using Downs and Blacks (DB) checklist (maximum quality score of 27). Aggregate data analysis and Student's t-test were performed for all identified studies (model A). For studies that published analysable Kaplan-Meier curves, survival data were extracted and marginal proportional hazards models were constructed (model B).
A total of 56 studies were identified and included in model A, 26 of which had analysable Kaplan-Meier curves and were included in model B. The 26 studies in model B had significantly higher mean DB scores than the remaining 30 (17.3 vs 13.7, P=0.002). For patients receiving first line chemotherapy, the estimated median OS was 15.7 months by model A (95% CI, 12.3-19.1), and 19.3 months by model B (95% CI, 17.6-21.1). For patients undergoing second line or higher therapies (2nd+), the estimated median OS was 11.5 months by model A (95% CI 10.1-12.9), and 12.5 months by model B (95% CI 11.9-13.4). PFS estimates for patients undergoing first-line chemotherapy by model A was 7.6 months (95% CI, 6.2-9.0), and 8.0 months by model B (95% CI, 7.6-8.8). For patients undergoing therapy in the 2nd+ setting, the estimated PFS by model A was 5.4 months (95% CI, 3.8-7.0), and 5.2 months by model B (95% CI, 4.7-5.6).
We present the first aggregate estimates of OS and PFS for RM-NPC patients receiving first and second-line or higher treatment settings, which could inform the design of future clinical trials in this disease setting.
大多数已发表的复发性或转移性鼻咽癌(RM-NPC)研究都是单臂试验。因此,很难对无进展生存期(PFS)和总生存期(OS)结果进行可靠建模。本研究旨在分析现有文献,以评估RM-NPC中现有全身治疗方案的相对疗效,并提供总OS和PFS的估计值。
我们对MEDLINE、EMBASE和Cochrane图书馆进行了系统检索,截至2015年3月。纳入了仅使用英文的、研究细胞毒性和分子靶向药物治疗成年RM-NPC患者的临床试验。所有相关研究均使用唐斯和布莱克(DB)检查表进行质量评估(最高质量评分为27分)。对所有纳入研究进行汇总数据分析和学生t检验(模型A)。对于发表了可分析的Kaplan-Meier曲线的研究,提取生存数据并构建边际比例风险模型(模型B)。
共识别出56项研究并纳入模型A,其中26项具有可分析的Kaplan-Meier曲线并纳入模型B。模型B中的26项研究的平均DB评分显著高于其余30项研究(17.3对13.7,P=0.002)。对于接受一线化疗的患者,模型A估计的中位OS为15.7个月(95%CI,12.3-19.1),模型B为19.3个月(95%CI,17.6-21.1)。对于接受二线或更高线治疗(2线及以上)的患者,模型A估计的中位OS为11.5个月(95%CI,10.1-12.9),模型B为12.5个月(95%CI,11.9-13.4)。模型A对接受一线化疗患者的PFS估计为7.6个月(95%CI,6.2-9.0),模型B为8.0个月(95%CI,7.6-8.8)。对于接受2线及以上治疗的患者,模型A估计的PFS为5.4个月(95%CI,3.8-7.0),模型B为5.2个月(95%CI,4.7-5.6)。
我们首次给出了接受一线和二线或更高线治疗的RM-NPC患者的总生存期和无进展生存期的汇总估计值,这可为该疾病背景下未来临床试验的设计提供参考。