ImportanceAlthough 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.ObjectiveTo determine if the approval of precision oncology therapies has benefited patients with cancer from various ancestral backgrounds equally over time.Design, Setting, and ParticipantsA 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.Main Outcomes and MeasuresFor 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.ResultsOverall, 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.Conclusion and RelevanceThis 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.

中文翻译：

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基于生物标志物的精准肿瘤治疗资格中基于遗传血统的差异


重要性尽管癌症患者关键癌症特异性体细胞突变的患病率作为遗传血统的函数的差异已经得到证实，但很少有研究解决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。目的确定精准肿瘤疗法的批准是否随着时间的推移平等地使来自不同祖先背景的癌症患者受益。设计、设置和参与者对 2014 年 1 月至 2022 年 12 月期间使用可操作癌症靶点的综合突变分析 （MSK-IMPACT） 测定法接受临床测序的实体癌患者的样本进行了回顾性分析。计算了 1998 年 1 月至 2023 年 12 月期间 FDA 药物批准的每个祖先群体中具有至少 1 个 1 级生物标志物的患者的年比例。分析于 2024 年 1 月开始。主要结果和措施对于每位患者，定量推断遗传血统，并根据主要参考血统对患者进行分组。OncoKB 用于识别每个肿瘤样本中所有与 FDA 批准的疗法相关的美国食品和药物管理局 （FDA） 认可的体细胞生物标志物（1 级生物标志物）。结果总体而言，该研究包括 59 433 例患者。2013 年，EGFR-酪氨酸激酶抑制剂厄洛替尼被批准用于 EGFR 突变肺癌患者，东亚和南亚血统的患者不成比例地受益，导致与其他人群相比，这些祖先群体中具有 1 级生物标志物的患者比例更高。 尽管 2019 年至 2020 年精准肿瘤药物批准的增加对欧洲血统患者的临床可操作性产生了显着的积极影响，但与 2019 年以来的其他群体相比，非洲血统患者的 1 级生物标志物比例最低。结论和相关性本研究系统评估和比较了基于基因组生物标志物的精准肿瘤治疗资格的时间变化，作为从 DNA 测序数据得出的推断遗传祖先的函数。尽管在过去十年中 FDA 对精准肿瘤疗法的批准率加快，但患者祖先群体之间基于生物标志物的药物资格存在可衡量的差异。由于非洲血统患者在获得癌症护理方面存在缺陷，这些差异可能会加剧非洲血统患者临床结果的系统性差异。