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What is Precision Medicine? Comprehensive genomic profiling

What is precision medicine?

Precision medicine

Precision medicine is about the personalisation of treatment

As our knowledge increases around the specific genomic alterations in cancer, treatment options can now be more personalised, based on the assessment of molecular alterations identified from a specific tumour rather than simplistically based on the cancer site.1–3

Cancer care is becoming increasingly complex;4–8 in 2017, there were over 700 molecules in late-stage development, almost 90% of which were targeted treatments.9 An evolving approach is required to manage this increasing complexity and realise the potential of precision medicine.4,10,11

The shift towards precision medicine12,13

Organ Based Biomarker Stratified Precision Medicine Chemotherapy Cancer is treated primarily according to its location in the body Personalised Treatment Molecular insights enable treatment to be personalised to the unique genomic profile  of a patient’s tumour Targeted Medicines Cancer therapy is selected based on both organ and biomarker 1990 2000 2010 2020 2030 1980
Genomic Insights

Genomic insights can help to identify targeted treatment options for patients

There are four main classes of genomic alterations14

03_precision medicine_02_genomic insights_v2RearrangementsCopy number alterationsInsertionsand deletions Basesubstitutions Four main classes of genomic alterations

How can we be sure an alteration doesn’t get missed? Single biomarker tests, using common diagnostic techniques such as polymerase chain reaction (PCR) / immunohistochemistry (IHC) / fluorescence in situ hybridisation (FISH), and multigene hotspot next-generation sequencing (NGS) tests may not be able to capture all of the known genomic alterations that may be used to guide patients’ treatment plans.4,15–17

Furthermore, complex pan-tumour biomarkers or ‘genomic signatures’, such as tumour mutational burden (TMB) and microsatellite instability (MSI), may help to identify if patients will respond well to specific targeted therapies. MSI (indicated by defective mismatch repair) has been shown to predict response to immunotherapy and TMB is emerging as a potential biomarker for enriched clinical benefit with immunotherapy.18–25 TMB and MSI can be measured effectively when used together with comprehensive genetic profiling (CGP) of the tumour genome.19,26

Roche Foundation Precision Tumour mutational burden Microsatellite instability MSI TMB
Evolving Approach

An evolving approach to ensure the right treatment for the right patient at the right time

Ensuring that patients with cancer can benefit from all available treatment options requires an evolving approach to clinical diagnostics and decision-making. This approach should:4,12

✓  Identify clinically relevant genomic alterations and signatures

✓  Provide clear, detailed information to aid clinical decision-making

✓  Inform the patient’s personalised treatment plan

CGP is important to ensure patients can benefit from the latest treatment innovations.1,10,19

Actionability of genomic profiling

Actionability is a broad concept and is often defined differently for individual studies and when used by clinicians. Actionability is generally defined as the extent to which genomic information has the potential to affect treatment decisions.27 Oncologists need to be able to distinguish between genomic profile findings that represent proven clinical value (can be directly actioned) or those that offer potential value (treatment options may not be accessible or approved in clinical practice). Some reporting systems may include hypothetical targets, drug targets that have proven efficacy but are not approved in the cancer type being investigated or may not clearly prioritise the target of most clinical value for the patient (due to poor definitions).28

It is important to determine what an ‘actionable’ mutation really means when listed in a profiling report.

Clinically actionable treatments identified from a patient profiling report include:29

The prescription of an approved treatment The opportunity to participate in a clinical trial

Breast and lung cancers are considered much more ‘actionable’ than other cancers, due to the high number of targeted treatments approved in these settings.30

The National Health Service (NHS) in England recognises precision medicine as a tailored approach that could better manage patients’ health and outcomes through the use of targeted therapies. By bringing together technologies such as genome sequencing, personalised data and wearable technology, the NHS hopes to enter an era of truly personalised care, which is embedded into mainstream healthcare.31

Personalised care Wearable technology Personalised data Genome sequencing

The National Comprehensive Cancer Network (NCCN) panel recommends testing for all key established biomarkers in patients with certain cancer types before initial treatment in the US, due to the effective targeted therapies and immunotherapies available.32

“The NCCN Panel strongly advises broader molecular profiling (also known as precision medicine)”

NCCN Guidelines for non-small cell lung cancer Version 5. 2018, last accessed January 2019:32

“Multiplexed genetic sequencing panels are preferred where available over multiple single gene tests to identify other treatment options beyond EGFR, ALK, BRAF, and ROS1.”

American Society of Clinical Oncology endorsement of the following guidelines for lung cancer, 2018:33

·      Association for Molecular Pathology

·      College of American Pathologists

·      International Association for the Study of Lung Cancer

Learn more about CGP Learn more about CGP

M-GB-00001593 September 2020
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