What approach should be taken for personalised medicine in oncology?

From the Guidelines

Personalized medicine in oncology should adopt a comprehensive approach that integrates genomic profiling, biomarker testing, and patient-specific factors to tailor treatment plans, as supported by the most recent evidence from 2024 1.

Key Considerations

• Oncologists should begin with comprehensive molecular testing of tumor samples, including next-generation sequencing to identify actionable mutations such as EGFR, ALK, BRAF, HER2, and BRCA.
• Treatment selection should then match specific drugs to these molecular targets - for example, osimertinib (80mg daily) for EGFR mutations in lung cancer, pembrolizumab (200mg IV every 3 weeks) for high PD-L1 expression tumors, or olaparib (300mg twice daily) for BRCA-mutated ovarian cancer.
• This approach should be dynamic, with regular monitoring of treatment response using both imaging and liquid biopsies to detect emerging resistance mechanisms.
• Patient factors including age, comorbidities, performance status, and preferences must inform treatment decisions, as should pharmacogenomic testing to predict drug metabolism and potential toxicities.

Rationale

The use of multi-omics data and AI is enabling the processing and understanding of intricate biological information on an unprecedented scale, leading to a rise in personalized medicine 1. According to the Personalized Medicine Coalition, the proportion of FDA-approved personalized medicines has escalated from 5% of total approvals in 2005 to 42% in 2019, with expected continuous growth 1. The market for personalized medicine is projected to grow from $300 billion in 2021 to $870 billion in 2031, indicating a substantial shift towards personalized approaches in healthcare 1.

Supporting Evidence

• A study from 2018 highlighted the importance of biomarker testing in non-small cell lung cancer, including EGFR, ALK, and ROS1 rearrangements, to guide treatment decisions 1.
• The 2023 St Gallen International Consensus Conference for the primary therapy of individuals with early breast cancer emphasized the need for a personalized approach, taking into account specific factors such as clinical stage, biological features of the tumor, and patient preferences 1.
• The development of novel treatments, such as Vitrakvi (larotrectinib) and Zolgensma (onasemnogene abeparvovec-xioi), has demonstrated the potential of personalized medicine in improving patient outcomes 1.

Conclusion is not allowed, so the answer ends here.

From the FDA Drug Label

Patient Selection for Single-Agent Treatment Select patients for treatment with KEYTRUDA as a single agent based on the presence of positive PD-L1 expression in: For the MSI-H/dMMR indications, select patients for treatment with KEYTRUDA as a single agent based on MSI-H/dMMR status in tumor specimens For the TMB-H indication, select patients for treatment with KEYTRUDA as a single agent based on TMB-H status in tumor specimens

The approach for personalised medicine in oncology should be based on biomarker testing, such as:

• PD-L1 expression
• MSI-H/dMMR status
• TMB-H status to select patients for treatment with pembrolizumab (2) (2).

Key considerations include:

• Using FDA-approved tests for patient selection
• Selecting patients based on the presence of specific biomarkers
• Considering combination therapy for certain indications

From the Research

Personalised Medicine in Oncology

The approach to personalised medicine in oncology involves tailoring treatment to individual patients based on their unique genetic profiles and molecular characteristics of their tumours.

• This approach has been shown to improve patient prognosis and quality of life by targeting specific molecular abnormalities in various types of cancer, such as breast cancer, colorectal cancer, and non-small-cell lung cancer 3.
• The use of next-generation sequencing (NGS) has revolutionized the field of personalised medicine in oncology, enabling the identification of novel targetable mutations and predicting the emergence of drug resistance 4, 5.

Role of Genetic Sequencing in Personalised Medicine

Genetic sequencing testing has become widely used to inform treatment decisions for advanced non-small-cell lung cancer patients.

• A study found that targeted DNA sequencing of 380 cancer-related genes identified actionable genetic alterations in 31% of patients who had no EGFR and ALK alterations on routine molecular tests 6.
• The results of targeted DNA sequencing testing can provide improved treatment options for some NSCLC patients and result in a survival benefit for those treated with targeted therapy 6.

Patient Understanding and Acceptance of Personalised Medicine

Patient and public understanding of the concept of personalised medicine is crucial for its successful implementation in healthcare systems.

• A systematic review found that patients have a greater understanding of and trust in personalised medicine compared to members of the public, but often misunderstand how genomic testing works 7.
• Key areas that can be targeted to inform future health literacy interventions include genetic literacy for the public and understanding of how personalised medicine testing and treatment works for patients 7.