Genetic Ancestry-Based Differences in Biomarker-Based Eligibility for Precision Oncology Therapies.

IMPORTANCE

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.

OBJECTIVE

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.

MAIN OUTCOMES AND MEASURES

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.

RESULTS

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.

CONCLUSION AND RELEVANCE

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.