Arora Kanika, Suehnholz Sarah P, Zhang Hongxin, Ostrovnaya Irina, Kundra Ritika, Nandakumar Subhiksha, Nissan Moriah H, Brannon A Rose, Bandlamudi Chaitanya, Ladanyi Marc, Drilon Alexander, Brown Carol L, Solit David B, Schultz Nikolaus, Berger Michael F, Chakravarty Debyani
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
JAMA Oncol. 2025 Mar 1;11(3):310-316. doi: 10.1001/jamaoncol.2024.5794.
Although differences in the prevalence of key cancer-specific somatic mutations as a function of genetic ancestry among patients with cancer has been well-established, few studies have addressed the practical clinical implications of these differences for the growing number of biomarker-driven treatments.
To determine if the approval of precision oncology therapies has benefited patients with cancer from various ancestral backgrounds equally over time.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of samples from patients with solid cancers who underwent clinical sequencing using the integrated mutation profiling of actionable cancer targets (MSK-IMPACT) assay between January 2014 and December 2022 was carried out. The annual fraction of patients per ancestral group with at least 1 level 1 biomarker was calculated for FDA drug approvals from January 1998 to December 2023. Analysis began in January 2024.
For each patient, genetic ancestry was quantitatively inferred, and patients were grouped based on predominant reference ancestry. OncoKB was used to identify all Food and Drug Administration (FDA)-recognized somatic biomarkers associated with FDA-approved therapies (level 1 biomarkers) in each tumor sample.
Overall, the study included 59 433 patients. The approval of the EGFR-tyrosine kinase inhibitor erlotinib for patients with EGFR-mutant lung cancers in 2013 disproportionately benefited patients of East Asian and South Asian ancestries, leading to higher patient fractions with level 1 biomarkers in these ancestral groups compared with other populations. Although the increase in precision oncology drug approvals from 2019 to 2020 had a notable positive impact on clinical actionability for patients of European ancestry, patients of African ancestry had the lowest fraction of level 1 biomarkers compared with other groups from 2019 onward.
This study systematically assessed and compared temporal changes in genomic biomarker-based eligibility for precision oncology therapies as a function of inferred genetic ancestry derived from DNA sequencing data. Despite the accelerated rate of FDA approvals for precision oncology therapies over the past decade, measurable differences in biomarker-based drug eligibility among patient ancestral groups exist. These differences may exacerbate the systemic disparities in clinical outcomes in patients of African ancestry due to existing deficiencies in their access to cancer care.
尽管癌症患者中关键癌症特异性体细胞突变的患病率因遗传血统而异已得到充分证实，但很少有研究探讨这些差异对越来越多的生物标志物驱动治疗的实际临床意义。
确定精准肿瘤学疗法的获批是否随着时间的推移平等地惠及了来自不同祖先背景的癌症患者。
设计、背景和参与者：对2014年1月至2022年12月期间使用可操作癌症靶点综合突变分析（MSK-IMPACT）检测进行临床测序的实体癌患者样本进行回顾性分析。计算了1998年1月至2023年12月美国食品药品监督管理局（FDA）药物获批时每个祖先群体中至少有1个1级生物标志物的患者的年度比例。分析于2024年1月开始。
对每位患者定量推断遗传血统，并根据主要参考血统对患者进行分组。使用OncoKB识别每个肿瘤样本中与FDA批准的疗法相关的所有美国食品药品监督管理局（FDA）认可的体细胞生物标志物（1级生物标志物）。
总体而言，该研究纳入了59433名患者。2013年表皮生长因子受体（EGFR）酪氨酸激酶抑制剂厄洛替尼获批用于EGFR突变型肺癌患者，这使东亚和南亚血统的患者受益过多，导致这些祖先群体中具有1级生物标志物的患者比例高于其他人群。尽管2019年至2020年精准肿瘤学药物获批数量的增加对欧洲血统患者的临床可操作性产生了显著的积极影响，但自2019年起，非洲血统患者的1级生物标志物比例与其他群体相比是最低的。
本研究系统评估并比较了基于基因组生物标志物的精准肿瘤学疗法适用资格随时间的变化，该变化是根据从DNA测序数据推断出的遗传血统而定。尽管过去十年FDA对精准肿瘤学疗法的批准速度加快，但患者祖先群体之间基于生物标志物的药物适用资格仍存在可测量的差异。由于非洲血统患者在获得癌症治疗方面存在现有不足，这些差异可能会加剧他们临床结局中的系统性差异。
