The shift towards precision medicine
Clinical practice is shifting towards an era of precision medicine where molecular insights enable treatment to be personalised to the unique genomic profile of a patient’s tumour.1–3 Cancer care is increasingly complex as more targetable genes are identified and treatment choice grows;4–8 in 2018, there were over 849 molecules in late-stage development, 91% of which were targeted treatments.9 An evolving approach to clinical diagnostics and decision-making is required if we are to manage this increasing complexity and realise the potential of precision medicine.4,10
Capturing clinically relevant genomic insights
There are four main classes of genomic alterations: base substitutions, insertions or deletions, copy number alterations and gene rearrangements. But are current diagnostic approaches up to the task of identifying them all? Single biomarker tests, using common diagnostic techniques such as PCR/IHC/FISH, and multigene hotspot NGS tests risk missing genomic alterations that may be critical to patients’ treatment plans.4,11–13
Furthermore, complex pan-tumour genomic signatures, such as Tumour Mutational Burden (TMB), blood Tumour Mutational Burden (bTMB) and Microsatellite Instability (MSI), may provide further valuable insights to help personalise treatment plans. MSI informs eligibility for immunotherapy and is a cancer guideline-recommended signature.14–18 TMB and bTMB are exploratory genomic signatures that inform eligibility for immunotherapies independently of PD-L1 expression.19–24 Comprehensive genomic profiling is the only viable routine clinical option for measuring TMB and bTMB.19–22
An evolution in diagnostics and clinical decision-making
Ensuring that cancer patients can benefit from the latest treatment innovations requires an evolving approach to clinical diagnostics and decision-making, one that:
✓ Identifies clinically relevant genomic alterations and signatures
✓ Provides clinical decision-making support
✓ Personalises patients’ treatment plans
Comprehensive genomic profiling is important to ensure patients can benefit from the latest treatment innovations.1,10,25
“The NCCN NSCLC Guidelines panel strongly advises broader molecular profiling with the goal of identifying rare driver mutations for which effective drugs may already be available, or to appropriately counsel patients regarding the availability of clinical trials. Broad molecular profiling is a key component of the improvement of care of patients
“Multiplexed genetic sequencing panels are preferred where available over multiple single gene tests to identify other treatment options beyond EGFR, ALK, BRAF and ROS1.”
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- Global Oncology Trends Report 2018. Report by IQVIA Institute for Human Data Science. Available at: https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/global-oncology-trends-2019.pdf (Accessed August 2021).
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- NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 2.2020, May 2020. Available at: https://www.nccn.org/guidelines (Accessed August 2020).
- FDA approves pembrolizumab for first-line treatment of MSI-H/dMMR colorectal cancer. Available at: www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-first-line-treatment-msi-hdmmr-colorectal-cancer (Accessed August 2021).
- FDA approves pembrolizumab for adults and children with TMB-H solid tumors, 2020. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors (Accessed August 2021).
- Gandara DR et al. Nat Med 2018; 24: 1441–1448.
- Yarchoan M et al. JCI Insight 2019; 4: e126908.
- Marabelle A et al. Ann Oncol. 2019;30(suppl_5):v475-v532.
- Socinski M. Ann Oncol 2019; 30(suppl_5): v851–v934.
- Khagi Y et al. Clin Cancer Res 2017; 23: 5729–5736.
- NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. Version 6.2020, June 2020. Available at: https://www.nccn.org/guidelines (Accessed August 2020).
- Kalemkerian GP et al. J Clin Oncol 2018; 36: 911–919.
- Lindeman NI et al. J Mol Diagn 2018; 20: 129–159.