Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.
Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Canada.
Oncologist. 2019 Jul;24(7):e518-e525. doi: 10.1634/theoncologist.2018-0808. Epub 2019 Mar 4.
Enrichment of patients based on molecular biomarkers is increasingly used in early phase clinical trials. Molecular profiling of patients with advanced cancers can identify specific genomic alterations to inform decisions about investigational treatment(s). Our aim was to evaluate the outcomes of new patient referrals to a large academic solid tumor phase I clinical trial program after the implementation of molecular profiling.
Retrospective chart review of all new referrals to the Princess Margaret Cancer Centre (PM) phase I clinic from May 2012 to December 2014. Molecular profiling using either MALDI-TOF hotspot mutation genotyping or targeted panel DNA sequencing was performed for patients at PM or community hospitals through the institutional IMPACT/COMPACT trials.
A total of 971 new patient referrals were included for this analysis. Twenty-seven percent of referrals assessed in clinic were subsequently enrolled in phase I trials. Of all new referrals, 41% had prior molecular profiling, of whom 11% ( = 42) were enrolled in genotype-matched trials. Patients with prior molecular profiling were younger, more heavily pretreated, and had more favorable Princess Margaret Hospital Index (PMHI) scores. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 ( = .002), internal referrals within PM ( = .002), and PMHI ( ≤ .001) were independently associated with successful trial enrollment in multivariable analysis.
Although nearly half of new patients referred to a phase I clinic had prior molecular profiling, the proportion subsequently enrolled into clinical trials was low. Prior molecular profiling was not an independent predictor of clinical trial enrollment.
The landscape of oncology drug development is evolving alongside technological advancements. Recently, large academic medical centers have implemented clinical sequencing protocols to identify patients with actionable genomic alterations to enroll in therapeutic clinical trials. This study evaluates patient referral and enrollment patterns in a large academic phase I clinical trials program following the implementation of a molecular profiling program. Performance status and referral from a physician within the institution were associated with successful trial enrollment, whereas prior molecular profiling was not an independent predictor.
基于分子生物标志物的患者富集在早期临床试验中越来越多地被使用。对晚期癌症患者进行分子谱分析可以确定特定的基因组改变，从而为治疗方案提供信息。我们的目的是评估在实施分子谱分析后，向一个大型学术实体肿瘤 I 期临床试验项目新患者转介的结果。
回顾性分析了 2012 年 5 月至 2014 年 12 月期间向玛格丽特公主癌症中心（PM）I 期临床诊所新转介的所有患者的病历。通过机构 IMPACT/COMPACT 试验，在 PM 或社区医院对患者进行基质辅助激光解吸电离飞行时间（MALDI-TOF）热点突变基因分型或靶向面板 DNA 测序的分子谱分析。
共纳入 971 例新患者进行分析。在诊所评估的 27%的转介患者随后被纳入 I 期试验。在所有新转介患者中，41%的患者有既往分子谱分析，其中 11%（=42）患者入组了基因匹配试验。有既往分子谱分析的患者更年轻，预处理更多，且 PM 医院指数（PMHI）评分更高。东部肿瘤协作组（ECOG）表现状态 0-1（=0.002）、PM 内部转介（=0.002）和 PMHI（≤0.001）在多变量分析中独立与成功入组试验相关。
尽管近一半向 I 期诊所转介的新患者有既往分子谱分析，但随后入组临床试验的比例较低。既往分子谱分析不是临床试验入组的独立预测因素。
肿瘤药物开发的格局正在随着技术进步而发展。最近，大型学术医疗中心已经实施了临床测序方案，以识别具有可操作基因组改变的患者，从而入组治疗性临床试验。本研究评估了在实施分子谱分析方案后，一个大型学术 I 期临床试验项目中患者的转介和入组模式。表现状态和机构内医生的转介与成功入组试验相关，而既往分子谱分析不是独立的预测因素。
