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

Area of Science:

• Genomic medicine
• Cancer genomics
• Health equity

Background:

• Genetic ancestry influences cancer somatic mutations, impacting targeted therapy eligibility.
• Few studies have explored the clinical implications of these differences for precision oncology.

Purpose of the Study:

• To assess if precision oncology therapies benefit diverse ancestral groups equally over time.
• To analyze temporal trends in biomarker eligibility across different genetic ancestries.

Main Methods:

• Retrospective analysis of 59,433 solid cancer patients' clinical sequencing data (MSK-IMPACT, 2014-2022).
• Inferred genetic ancestry and identified Food and Drug Administration (FDA)-recognized level 1 biomarkers using OncoKB.
• Calculated annual fractions of patients with biomarkers per ancestral group relative to FDA drug approvals (1998-2023).

Main Results:

• The EGFR inhibitor erlotinib disproportionately benefited East and South Asian ancestries.
• Precision oncology drug approvals (2019-2020) improved eligibility for European ancestry patients.
• Patients of African ancestry consistently had the lowest fraction of level 1 biomarkers from 2019 onward.

Conclusions:

• Significant disparities exist in biomarker eligibility for precision oncology therapies across ancestral groups.
• These differences may worsen existing health outcome disparities for patients of African ancestry.
• Systematic assessment of genomic data by ancestry is crucial for equitable cancer care.