Employing Comprehensive Genomic Testing in the NSCLC Paradigm

Hatim Husain, MD, spoke with CancerNetwork^® regarding the use of comprehensive genomic profiling, specifically for patients with non–small cell lung cancer (NSCLC). Husain, a professor in the Department of Medicine at the University of California San Diego, touched on the NCCN guidelines, the testing evolution with more personalized treatments, and the impact of treatment decisions when a comprehensive genomic profile has not been completed. A few of the available genomic profiling tests in the space include FoundationOne CDx, Guardant360, and PanTracer.

FoundationOne CDx is a tissue-based test, with an FDA approval for patients with EGFR exon 19 deletion and EGFR exon 21 L858R alterations, EGFR exon 20 T790M alterations, ALK rearrangements, and BRAF V600E mutations, among others.¹ The test analyzes guideline-recommended genes across all solid tumors.

Guardant360 liquid and tissue tests both assess for covered guideline-recommended biomarkers for common cancer types.² For lung cancer, this includes ALK, BRAF, EGFR, ROS1, KRAS, and MET, among others. For tissue testing, it identifies 740 genes, 360 RNA fusions, and 19,000 epigenomic signals. For liquid, it identifies 740 genomic biomarkers and 19,0000 epigenomic signals and has a turnaround time of 7 days.

PanTracer looks at both tissue and liquid testing options, including broad, guideline-specific comprehensive genomic profile panels, with a turnaround time of 8 to 10 days for tissue and 7 days for liquid.³ This profile also provides concise reports of the findings and requires minimal specimen requirements. The tissue test assesses 517 genes and assesses DNA and RNA for fusion detection. The liquid test looks for 514 genes and circulating tumor DNA (ctDNA) sequencing from blood samples and is a better option if tissue testing fails for the patient or is unavailable.

Additionally, there is the PanTracer Tissue + HRD test that looks at comprehensive genomic profiles with a homologous recombination deficiency assessment. This will assess BRCA1/2 and genomic instability scores, which include the loss of heterogeneity, telomeric allelic imbalance, and large-scale state transitions. Overall, this will allow for more personalized treatment decisions.

Q / Why is comprehensive genomic testing a critical part of oncology care?

Husain / Molecular profiling is an essential part of clinical care for most patients with solid tumors. One of the cancers that I treat most commonly is lung cancer. In the disease of lung cancer, we need to know the genotype of almost all patients with NSCLC, and if we look at nonsquamous NSCLC, all patients have the potential opportunity to have a genomic marker. In our practice, we are testing all patients with NSCLC for actionable genomic alterations. Some of the common technologies that are available to clinicians that we use in our practice are both tissue testing for molecular profiling and plasma-based testing with next-generation sequencing. Some of the key reasons for this are identifying actionable targets and genomic drivers early and up front to guide patient decision-making for advanced cancers. We have also been using comprehensive genomic testing at different points in a patient’s care at the time of progression, and this has particularly been useful for resistance monitoring to identify the reasons why cancer may increase and what genomic details are important for that event.

Q / How should clinicians approach using samples they might already have for comprehensive genomic profiling?

Husain / With the growing recognition of the value of comprehensive genomic profiling, we have integrated an approach that looks at liquid and tissue samples in a more complementary fashion. Specifically, this becomes important in the context of tissue. If tissue is insufficient or not feasible, with the turnaround time that is necessary for a patient, plasma may be particularly facilitatory in identifying genomic alterations early and up front to help guide the first-line management for a patient. Additionally, when plasma is inadequate, and that is specifically in circumstances of low tumor fraction, tissue testing may be needed to make sure that we are finding all mutations that are relevant for a patient and reducing the opportunity for false-negative results. In my view, we think about using tissue and liquid more in a complementary fashion, understanding the needs and application of each and what is particularly relevant for the patient at the time that we are seeing them.

Q / What are the current NCCN guidelines for using comprehensive genomic profiling for patients with metastatic advanced NSCLC? Looking toward the community, do you see guideline adherence?

Husain / It’s important to note that the NCCN has provided recommendations for comprehensive genomic profiling when it comes to the management of metastatic NSCLC. There is guidance about when and how to think about using plasma in relation to tissue samples, the pros and the cons, as well as when plasma may need reflexive tissue or a tissue sample to provide the opportunity not to miss a result. Particularly, that’s in the context of a low tumor fraction, where there may not be enough DNA in the plasma at that time, and relying on the tissue becomes more important. From my perspective, I do see that adherence to guidelines in the community is increasing. I’ve been particularly impressed by the fact that over time, there have been improvements in meeting unmet needs for broader adherence. I do think that there are enough. There are opportunities to improve. However, this relies on how we think about the appropriate workflows and education that are necessary about each genomic target and its relevance in ways to streamline the clinic flow to be able to achieve the testing process and complete that. I’m quite hopeful that through time, we will see further increases in adherence in the community.

Q / Looking at your clinical practice, are there platforms or laboratories where you use test types that you have found to be most impactful in terms of workflow? What are the benefits offered?

Husain / With our practice, we have used comprehensive genomic profiling to help guide treatment decisions for patients, and some of the things that we have found particularly useful are those panels that include all the relevant genomic targets and even ones that may be important for resistance. Some of the technologies that we routinely use provide information about events that may be relevant for what’s known as clonal hematopoiesis. This is relevant in the context of liquid biopsies, where some genomic alterations found in plasma may not be coming from the tissue and, in fact, may be coming from white blood cells or leukocytes. Having a good framework to understand which alterations are coming from the tumor and which alterations are coming from white blood cells is an important area to think through. This has been made easier with certain technologies that are provided in the reports.

Importantly, we have also been impressed by the ability to look for fusion events as well as point mutations and copy number gains and losses. There are some medicines that are being explored and have built approvals around copy number and how copy number is also an important factor in terms of representation, and our understanding of the appropriate driver events vs resistant profiles that can be seen in cancer is emerging and is an important factor in lung cancer. We are also thinking about technologies that can be used serially, and the opportunity to look at genomic events that may be changing over time is particularly relevant in understanding how resistance may occur for patients with cancer. We’ve been looking at technologies that can look at providing qualitative information on how the genome may change through time, how that gives us an understanding of the tumor burden that a patient may have, and how that relates to CT scans. We’re particularly hopeful and excited about the ways that new technologies have been approaching this field of cancer genomics and how they have been integrated with the current treatment paradigm.

Q / How can education about the benefits of concurrent liquid and tissue testing be improved? Are there particular approaches that you think will be the most effective in helping clinicians understand the impact of this testing?

Husain / Indeed, there is still a gap in the routine use of comprehensive genomic profiling, and I do feel that education is a core element here to help mitigate or bridge that gap. There needs to be better education on the clinical impact and value of identifying driver events for treatment selection. There also must be more education on the clinical value of the medicines for which these molecular profiles will help identify patients, and that goes hand in hand. More education on the technologies but also the downstream medicines that are applicable for patients in whom molecular profiles are well suited is a key point to better education and understanding turnaround time. The behind-the-scenes activities that are necessary to generate the test result are also helpful because they put into perspective and help in communicating with the patients the reasons why results may take time. Also, a greater awareness of a team approach [for] all members of the health care team about the importance of the genomic test results will help ensure that the process gets streamlined and that the workflow is optimized to be able to decrease the time to the test result. When the test result comes, [we need to ensure] that it’s easily visible and apparent to the whole health care team, who may rely on it for use. Some of the strategies that we’ve been thinking about are how to provide more education within our teams about genomic testing and its value and how we can think about the right workflows to ensure that the testing gets done quickly and efficiently.

Q / What is the impact of not having a comprehensive genomic profile, and how might that affect treatment decisions based on biomarkers? Alternatively, how has comprehensive testing positively affected care for patients with NSCLC?

Husain / From my perspective, there is a big impact of incomplete testing. What can result is the fact that a patient can be left behind without an option that may have otherwise helped them. Along those lines, we take every measure to make sure that adequate testing is performed with the intention that no patient is left behind without genomic testing done or a test result. Biomarker-driven decision-making is essential in metastatic lung cancer because we have first-line approvals for targeted therapy based on genomic drivers. There have been very clear examples of patients in whom comprehensive genomic profiling has positively impacted patients: deeper responses within cancer, faster responses, and more durable responses, which have improved survival compared with historical controls.

Q / What advice would you offer to oncologists looking to align with best practices?

Husain / Some of the strategies that we have implemented to try to align with [comprehensive genetic profiling] best practices are creating educational opportunities for staff to understand the importance of genomic testing, the importance of having results that are easily visible for the whole health care team, and making sure that the results are frequently and efficiently uploaded into our system in ways that we can continuously reflect on them through time. We’ve also worked hard to create a culture of accountability so that all are invested in understanding the importance of the test result and how we can work together to make sure that turnaround time can efficiently [occur]. We have spent time thinking through our electronic medical record on how we can label the appropriate genomic data so that they are easily identifiable in the chart. We have also educated patients about how to obtain their test results and provided workflows on how we can provide copies of the report, [with] words and better education for patients on the meaning of the molecular results that they’re obtaining. We’ve also been thinking through ways to scale this in an opportunity that, as testing is done over time, we can aggregate the test results and provide information to patients as comprehensive genomic profiling enters a monitoring phase, looking at tumor burden through time. With these strategies, we feel we’re at least taking initial steps to make sure that we are not missing an opportunity or leaving something behind in the context of testing that may improve outcomes for patients.

Q / How will comprehensive genomic profiling evolve as cancer care becomes more personalized?

Husain / Comprehensive genomic profiling will continue to become an essential part of delivering cancer care. It’ll continue to grow, and some of the ways it may grow are by serial testing, looking for resistance, monitoring, as well as tracking tumor burden. It may also enter into earlier stages of cancer, where now, based on the information for certain specific oncogenes, other oncogenes are being vetted for efficacy with targeted therapy in the early stage.

References

1. FoundationOne CDx. Foundation Medicine. Accessed August 5, 2025. https://tinyurl.com/bdh97f7x

2. Testing across the continuum of cancer. Guardant. Accessed August 5, 2025. https://tinyurl.com/mttamdyh

3. PanTracer portfolio. NeoGenomics. Accessed August 5, 2025. https://tinyurl.com/mu2fvsrb