Next Generation Sequencing (NGS), which is becoming more widely known as Comprehensive Genomic Profiling by Massively Parallel Sequencing (CGP), is set to significantly contribute to targeted therapy prescribing and complement other testing methods by 2020. Many genes are analysed simultaneously and it has the potential to detect all mutations in a patient specimen. However, the speed and spread of NGS uptake is not likely to revolutionise cancer care in this timeframe due to a number of challenges.
Incorporating NGS/CGP into the laboratory landscape, using non-small cell lung cancer (NSCLC) as an example
NGS/CGP is being adopted for NSCLC due to the complexity of the driver and resistance mutation tied to therapy options, and this is supported by NCCN and ESMO guidelines on broad molecular testing of NSCLC. There are two distinct groups of NGS/CGP panels emerging:
Smaller ~50 gene panels that are built with known actionable biomarkers
Larger 500+ to whole exome sequencing
NGS/CGP diffusion (the spread of the testing technology) is following a classic adoption curve:
Q2 2014 saw 24 US labs offering NGS/CGP testing
Q2 2017 saw 86 US labs offering NGS/CGP testing
Q2 2020 will see an estimated 200 US labs offering NGS/CGP testing
When looked at as a timeline we can see how the NGS/CGP landscape is developing. From 2013, we see oncology reference and research labs such as Foundation Medicine and Harvard get on board as ‘Early Adopters.’ LDTs dominate at this time and the FDA granted marketing authorization for Illumina’s MiSeqDx—the first NGS/CGP platform—and universal reagents.
From 2016-18, we have witnessed the ‘Early Followers’ become active. Larger commercial labs are supporting disease panels, for instance, in NSCLC. Initial clinical utility studies are published in breast cancer, melanoma and NSCLC, while the first NGS/CGP-based companion diagnostic (Rucaparib from Foundation Medicine) is FDA-approved in ovarian cancer.
From 2020, we anticipate NGS/CGP will become more mainstream. Medium volume oncology testing labs are likely to provide it in house rather than sending out to other labs. The volume of clinical utility studies will increase to support guideline development. And while a steady stream of FDA kits will be approved, LDTs will probably remain dominant.
Looking ahead to the 2022 landscape, we see the ‘Late Adopters’ appearing. As the cost of NGS/CGP platforms is destined to fall and reimbursement issues improve, community oncology facing labs will be able to include NGS/CGP on the menu.
Analytics for key disease areas illustrate the shape of the NGS/CGP Dx landscape
While the current diffusion of NGS/CGP varies by disease, laboratory type and geography, it is mainly centralized to large commercial reference labs and academic institutions. It is these key cancer reference labs that will continue to drive clinical utility and intellectual property for panels, shaping their NGS/CGP footprint to suit business strategy.
US data for NSCLC illustrates how NGS/CGP panels will be driven by clinical utility in key disease areas1:
84 labs have an in-house NGS/CGP test on offer for EGFR
85% of labs perform in-house NGS/CGP testing for both EGFR and ALK
No hospital labs perform in-house NGS/CGP testing for EGFR only
1 commercial lab performs in-house NGS/CGP testing for ALK only
Although EGFR and ALK, along with ROS1 and MET, are commonly part of NGS/CGP lung cancer panels, some laboratories do not include ALK as they have a more cost-efficient validated test.
Regarding platform adoption in the US, Illumina and ThermoFisher dominate the clinical space but there is now adequate competition to drive down platform costs. This will lead to greater choice for labs and thereby support diffusion in the longer term. For now, NGS/CGP-ready labs in the US continue to offer other test methods to support prescribing1, 2:
84 labs have an in-house NGS/CGP test on offer for EGFR
73 labs have an in-house RT-PCR test on offer for EGFR
28 labs have an in-house Sanger sequencing test on offer for EGFR
106 labs have an in-house FISH test on offer for ALK
72 labs have an in-house NGS test on offer for ALK
22 labs have an in-house IHC test on offer for ALK
Landscape and market diffusion outside the US
Outside the US, market diffusion will vary regionally depending upon smart investment in the main drivers (more information on these drivers here)1. Using BRAF testing in Europe as an example we see:
In Belgium, labs are using mainly Real-Time PCR and NGS/CGP methodologies, with more laboratories planning a shift towards NGS/CGP in the near future. This may result in issues with turnaround time (TAT) and reimbursement (which is available for BRAF testing in melanoma but only in metastatic disease).
In Switzerland, labs are trending toward the use of NGS/CGP for solid tissue mutational tests such as BRAF, with those labs that have not already validated an NGS/CGP test looking to do so. Moving towards NGS/CGP might increase due to new testing guidelines. TAT for BRAF is an average of one week (five days). Introduction of NGS/CGP might have contributed to the increase in time, but larger volumes of NGS/CGP-based tests might reduce this TAT to 3-4 days in the future.
In Sweden labs are using mainly Pyrosequencing, Real-Time PCR and NGS/CGP methodologies, with more laboratories planning a shift towards NGS/CGP in the near future, which may have an impact on TAT.
In other main markets diffusion will again vary depending on smart investment3.
Brazil has an NGS/CGP footprint but major labs offer limited or have access to NGS/CGP testing.
In China there is a rapidly expanding base of platforms due to considerable strategic investment by platform suppliers, in particular, Illumina.
India and Russia are still underdeveloped in NGS/CGP.
Viewing the overall landscape, incorporation of NGS/CGP to a point where it becomes a routine aspect of patient management will require further investment and, while very promising to see so much progress, this is still some time away.
Data from Diaceutics Laboratory Oncology Database
Analysis based on all labs validated methods. Labs have multiple methods therefore total lab number will exceed 151.