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Shifting the Paradigm: Broader Patient Access to Personalized Oncology Treatments Hinges on In-House Comprehensive Genomic Testing

We are living in an unprecedented time in the collective fight against cancer, where recent developments in drug development are giving rise to a new era of hope.  In 2018, the U.S. Food and Drug Administration (FDA) approved 59 novel therapies, breaking its record of 53 drugs back in 1996. The largest share of these approvals were for oncology.1 This new era is reinforced by the approval of the first pan-cancer drug, meaning it can be used to treat any kind of tumor with a specific molecular characteristic independent of where the tumor originated in the body.

Consequently, we are now beginning to see survival rates climb for certain cancer types globally, with expected improved health outcomes in the years to come. These important steps forward are enabled with the support from researchers who are continually making new discoveries that expand our knowledge of this multi-faceted disease as we push to make cancer a manageable chronic condition.

Overall, there are now more than 100 targeted therapies approved by the FDA as first-line or second-line options for multiple cancers. It is estimated that about 70 percent of novel drugs under development in oncology pipelines can be classified as “targeted therapies” that rely on genomic profiling to select eligible patients. Multi-biomarker-driven therapy selection is clearly the future of precision oncology.

While we have witnessed a tremendous surge in available cancer treatments, there is still a major hurdle hampering expeditious transfer of these therapies to patients: access to timely molecular testing results from next generation sequencing (NGS). In order for these drugs to benefit more patients, there needs to be a major paradigm shift in the way genomic profiles of patient tumors are generated, interpreted and provided to oncologists, particularly in the local hospital setting. It is clear that in order to expedite access to the full army of targeted therapies, NGS will have to go mainstream.

Under the current testing paradigm, valuable time – as much as four weeks – is required to obtain NGS results when tumor samples are sent to reference laboratories for molecular testing. During this time, it is commonplace for many physicians to take action and put their patients, who are typically in advanced stage of the disease, on some type of treatment regimen (e.g. I/O drugs). This decision is, unfortunately, based on limited information mostly derived from single-biomarker testing, such as PD-L1 status assessed via immunohistochemistry (IHC).

Often, treatment plans are later revised when NGS testing results become available to reveal, for example, that the patient’s tumor harbors a mutation in the EGFR or BRAF gene, which is not amenable to I/O drugs as a first-line treatment. This, of course, assumes results do come back at all, which does not happen in about 20% of cases due to high sample quantity requirements for testing by reference labs, according to a recent study2-5. But when results from comprehensive genomic testing are available and enable a treatment change in favor of a targeted therapy approach, it’s not as simple as switching to a new pill from one day to the next.

Patients are usually kept on the initial treatment for a full cycle before they are administered the potentially more-effective targeted therapy. There is also a wait time of at least two weeks between treatments in order to give time for the patient to eliminate remnants of the previous drug from their system and to recover from its side effects.

Additionally, the psychological stress for late-stage cancer patients to have to wait for weeks to receive test results that could inform a more-effective targeted therapy while they carry on with a potentially inferior treatment plan can be highly discouraging.

The paradigm shift in routine procedure that is needed to overcome this testing hurdle hinges on a solution that simplifies NGS and makes it easily adoptable by local hospitals. Eliminating the current complexity of NGS procedures and making it convenient for virtually any laboratory to operate is critical. The impact of having a fast, comprehensive and cost-effective in-house NGS solution that delivers results with minimal sample requirements could have an unprecedented benefit for thousands of cancer patients on a global scale.

Ideally, pathologists would have access to comprehensive genomic results for patients within days, not weeks. The ability for oncologists to then make a more informed treatment decision for their patients upfront should be the rule and not the rare exception.

While the possibility might seem far into the future, this paradigm shift is much closer than we think. NGS technology is rapidly evolving and becoming automated and easier to implement. The old days where operators needed a high level of proficiency to carry out NGS processes is quickly dissipating with powerful software that is now coming online.

When such a solution becomes common in the not too distant future, expedited patient access to the wide range of targeted therapies will finally be realized. I am looking forward to that day. Thanks to those who have been at the forefront of the battle against cancer – researchers, technology and drug developers – we can now begin to see a future in which this paradigm shift is possible.

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REFERENCES

1. FDA approves 19 new cancer drugs and biologics in 2018—and don’t forget two new endpoints and “real-time” review

2. Next-Generation Sequencing in 305 Consecutive Patents: Clinical Outcomes and Management Changes; Gregory J. Kubicek, MD., et al., Journal of Clinical Oncology, Aug. 2019.

3. First-Line Nivolumab Plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer (CheckMate 568): Outcomes by Programmed Death Ligand 1 and Tumor Mutational Burden as Biomarkers; Suresh S. Ramalingam, MD., et al., Journal of Oncology, Feb. 2019.

4. Clinical utility of FoundationOne tissue molecular profiling in men with metastatic prostate cancer; Jason Zhu, et al.; Urologic Cancer: Seminars and Original Investigations, July 2019.

5. Abstract 4889: Comparison of tumor mutational burden using the Ion Oncomine™ TML and FoundationOne™ assays with routine clinical FFPE tissue samples to predict durable clinical benefit in lung cancer and melanoma patients - a multivariate analysis integrating PD-L1 and CD8+ evaluation. Heeke S. et al. DOI: 10.1158/1538-7445.AM2019-4889; July 2019.

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Luca Quagliata, Ph.D.
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Luca Quagliata, Ph.D.

Luca Quagliata, PhD, is the global head of medical affairs for clinical NGS and oncology at Thermo Fisher Scientific. He is an adjunct faculty member for the Certificate of Advanced Study (CAS) in Personalized Molecular Oncology at the University of Basel and was previously the lab director at the Institute of Medical Genetics and Pathology at the University Hospital Basel, Switzerland.


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