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 based on the cancer site.1–3
Cancer care is becoming increasingly complex5–8. 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
Genomic insights can help to identify targeted treatment options for patients
There are four main classes of genomic alterations14
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 when used together with comprehensive genetic profiling (CGP) of the tumour genome.19,26
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).27
It is important to determine what an ‘actionable’ alteration really means when listed in a profiling report.
Clinically actionable treatments identified from a patient profiling report include:29
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
For NSCLC, genomic testing for EGFR, ALK, KRAS G12C, METex14 skipping, ROS1, NTRK, BRAF and RET is commissioned by the NHS in England, as specified in the National Genomic Test Directory.32
In lung cancer the NCCN, 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.33
“The NCCN Panel strongly advises broader molecular profiling (also known as precision medicine)”34
“Multiplexed genetic sequencing panels are preferred where available over multiple single gene tests to identify other treatment options beyond EGFR, ALK, BRAF, and ROS1.”35
American Society of Clinical Oncology endorsement of the following guidelines for lung cancer, 2018.36
· Association for Molecular Pathology
· College of American Pathologists
· International Association for the Study of Lung Cancer
CGP: comprehensive genetic profiling; FISH: fluorescence in situ hybridisation; IHC: immunohistochemistry; MSI: microsatellite instability; NHS: National Health Service; NGS: next-generation sequencing; NCCN: National Comprehensive Cancer Network; NHS: National Health Service; PCR: polymerase chain reaction; TMB: tumour mutational burden.
M-GB-00009116 April 2023
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- Hirsch FR, et al. Lancet. 2016;388:1012–1024.
- Baumgart M. Am J Hematol Oncol. 2015;11:10–13.
- Chakravarty D, et al. JCO Precis Oncol. 2017; doi: 10.1200/PO.17.00011.
- Global Oncology Trends Report 2022. Report by IQVIA Institute for Human Data Science. Available to download here Accessed November 2022.
- Gagan J and Van Allen EM. Genome Med. 2015;7:80.
- Love-Koh J, et al. PharmacoEconomics. 2018;36:1439–1451.
- Lukong KE, et al. BBA Clinical. 2017;7:64–77.
- American Society of Clinical Oncology. Cancer Progress Timeline. Available at: https://www.asco.org/research-guidelines/cancer-progress-timeline/
- Stratton MR, et al. Nature. 2009;458:719–724.
- Schrock AB, et al. Clin Cancer Res. 2016;22:3281–3285.
- Rankin A, et al. Oncologist. 2016;21:1306–1314.
- Suh JH, et al. Oncologist. 2016;21:684–691.
- Rizvi NA, et al. Science. 2015;348:124–128.
- Chalmers ZR, et al. Genome Med. 2017;9:34.
- Rosenburg JE, et al. Lancet. 2016;387:1909–1920.
- Goodman AM, et al. Mol Cancer Ther. 2017;16:2598–2608.
- Johnson DB, et al. Cancer Immunol Res. 2016;4:959–967.
- Rizvi H, et al. J Clin Oncol. 2018;36:633–641.
- Hellmann MD, et al. N Engl J Med. 2018;378:2093–2104.
- Le DT, et al. N Engl J Med. 2015;372:2509–2520.
- Hall MJ, et al. J Clin Oncol. 2016;30(15_suppl):1523.
- Mateo J, et al. Ann Oncol. 2018;29:1895–1902.
- National Cancer Institiute. Targeted Cancer Therapies Fact Sheet. May 2022 Available at https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies
- Schwaederle M, et al. Mol Cancer Ther. 2016;15:743–752.
- Wall DP and Tonellato PJ. F1000 Med Rep. 2012;4:14
- NHS England. Improving outcomes through personalised medicine. September 2016. https://www.england.nhs.uk/wp-content/uploads/2016/09/improving-outcomes-personalised-medicine.pdf
- NHS England. National Genomic Test Directory. October 2022. Available at https://www.england.nhs.uk/publication/national-genomic-test-directories/.
- Ettinger DS, et al. J Natl Compr Canc Netw. 2021;19(3):254-266
- NCCN Guidelines for non-small cell lung cancer Version 5. 2022, last accessed September 2022
- Kalemkerian et al., J Clin Oncol 2018;36(9):911-919
- Lindeman NI, et al. J Mol Diagn. 2018;20:129–159.