In an interview with PharmaShots, Kathryn Lang, Vice President, Outcomes & Evidence at Guardant Health shared her views on the data from the VALUE study of Guardant360 liquid biopsy test for NSCLC

Shots:

• The VALUE study evaluates the clinical outcomes & utility of liquid biopsy vs tissue biopsy testing in patients with NSCLC across six Canadian centers
• In an initial diagnosis, patients treated with Guardant360 liquid biopsy test along with traditional tissue testing showed an increase in targeted therapy use compared to tissue testing alone
• Guardant360 CDx test is 1st FDA-approved liquid biopsy for comprehensive genomic profiling for solid tumor cancers. Additionally, clinical studies of Guardant360 liquid biopsy are also underway with biopharma companies & aim to accelerate clinical trial enrollment by identifying patients with actionable biomarkers who benefit from targeted therapy

Tuba: Can you provide an overview of ‘The economic value of liquid biopsy for genomic profiling in advanced NSCLC’ study and its goals? What is the importance of presenting this data at WCLC?

Kathryn Lang: This cost-effectiveness analysis from the VALUE study (NCT03576937) investigated the clinical outcomes and utility of liquid biopsy for molecular profiling of patients with non-small cell lung cancer (NSCLC) at six Canadian centers. Liquid biopsy tests are minimally invasive compared to tissue biopsy testing, which is the current standard of care for patients with NSCLC.

The analysis presented at the World Conference on Lung Cancer (WCLC) demonstrated that when using the Guardant360 liquid biopsy test as well as traditional tissue testing in the initial diagnosis of patients with advanced NSCLC, this led to a significant increase in targeted therapy use compared to patients who received tissue testing alone. In addition, the use of liquid biopsy with tissue testing resulted in an estimated cost savings of over CAD 37,000 per patient to the health system, primarily by avoiding inappropriate use of chemo-immunotherapy as a first-line treatment.

Anytime new technology is integrated into the clinical care paradigm, there are questions about cost-efficacy and whether additional tests simply add cost to the system or if they provide greater economic benefit. This analysis underscores that adding liquid biopsy to tissue testing is a cost-effective way to identify actionable biomarkers easily and quickly, which allows clinicians to make informed treatment decisions for their patients with advanced cancer who benefit from starting on the right treatment right away.

Tuba: Can you explain the trial design and how you came to the results?

Kathryn Lang: This analysis focused on the cohort of patients from the VALUE study with newly diagnosed Stage IV non-squamous NSCLC with a limited smoking history (£10 pack-years). Blood samples were collected, and plasma-based comprehensive genomic profiling was conducted using the Guardant360 test. Standard-of-care molecular profiling of tissue specimens was also conducted per the sites’ standard practices. Clinical data were collected through the trial, including progression-free and overall survival figures. Cost information from the Princess Margaret Cancer Center and published literature were also used in the analysis including costs for targeted therapy, chemo-immunotherapy, and repeat tissue biopsy.

A decision-analytic Markov model from the perspective of the Canadian publicly funded healthcare system was used to compare tissue biopsy alone versus tissue biopsy plus the addition of liquid biopsy. This model considered the costs of the first-line treatment, testing, disease management, and terminal care. The model identified a cost savings of CAD 37,216 per patient adding liquid biopsy to standard tissue testing. A sensitivity analysis demonstrated that the majority of cost savings resulted from a greater number of patients receiving targeted therapy, rather than costly and potentially ineffective chemo-immunotherapy, as a result of liquid biopsy tests identifying actionable mutations.

Tuba: Can you explain the functionality of the Guardant360 test, including why it is important for the quality of treatment for NSCLC patients?

Kathryn Lang: The Guardant360 liquid biopsy provides comprehensive genomic profiling through plasma cell-free DNA. This test can shed light on genomic biomarkers relevant to clinical care through a simple blood draw, rather than requiring the traditional, invasive biopsy to obtain a tissue specimen. A simple blood draw is especially important for patients with NSCLC, as tissue samples are often scarce and difficult or dangerous to obtain. In addition, clinicians will get comprehensive genomic results from the Guardant360 liquid biopsy test in seven days or less, enabling them to start biomarker-informed treatment sooner than with the use of tissue testing. There are a growing number of guideline-recommended biomarkers to be tested in advanced NSCLC that can suggest paired targeted therapy options for patients, often with much higher efficacy and fewer toxicities compared to standard chemo-immunotherapy in those patients.

Tuba: Can you tell us more about the biomarkers accessed by Guardant Health during this trial, and how liquid biopsy may be preferable to tissue biopsy?

Kathryn Lang: The Guardant360 liquid biopsy tests for alterations in more than 70 genes associated with advanced solid tumors, including many that are guideline-recommended for assessment in advanced NSCLC: EGFR, ALK, KRAS, MET, BRAF, RET, ROS1, ERBB2, and NTRK. The types of alterations (single nucleotide variants, small insertion-deletion, copy number amplifications, and fusions) that are clinically relevant depend on the gene and cancer type. A comprehensive profiling solution is important in a disease like lung cancer where there are so many relevant biomarkers to examine. The non-invasive nature of liquid biopsy makes it a safe, convenient, and comfortable option for patients to access profiling information without having to undergo additional invasive biopsy procedures to procure sufficient specimens for tissue-based profiling of all the important biomarkers. The Guardant360 test is also very fast – many tissue profiling tests can take weeks to provide results if sample quantity is determined to be sufficient for testing, whereas the Guardant360Ò liquid biopsy can provide comprehensive genomic profiling in 7 days or less. Cutting down on the time it takes to get results is important for ensuring patients with advanced disease get on the most effective treatment as quickly as possible. 

Tuba: Can you please share some details about the different trials ongoing for Guardant360, and the future of this research?

Kathryn Lang: Guardant Health continues to evaluate the utility of its liquid biopsy tests and the benefit that these tests can bring to the treatment of patients with late-stage cancers.

Guardant Health has initiated the Guardant360 Related Clinical Outcomes in Patients Who Share Medical Records-Breast Cancer (GRECO-B) trial in June 2020. This 300-person observational study will evaluate the role Guardant360 ctDNA testing plays in determining a patient’s treatment plan and how well that treatment plan controlled their cancer.

The SOLTI 1903 HOPE study will assess the real-world clinical practice of integrating molecular profiling in the standard of care management of patients in Spain diagnosed with metastatic breast cancer who are receiving, have just received, or will receive treatment for their advanced disease. Tissue samples from metastatic or primary tumors will be collected for analyses, together with blood samples. A Molecular Advisory Board (MAB) will assess and give treatment recommendations, including clinical trials for which they may be eligible, based on the patient's molecular profile.

Clinical studies are also underway with biopharma companies using the Guardant360® liquid biopsy to accelerate clinical trial enrollment by identifying patients with actionable biomarkers who may benefit from the targeted therapy being evaluated in the clinical trial. One example of this is the Tepotonib Phase II in NSCLC Harboring MET Alterations (VISION), which has used the Guardant360 assay to identify patients with NSCLC who have the MET alteration to see if they may benefit from the targeted therapy tepotonib.

Guardant Health also has active clinical trials evaluating the clinical effectiveness of additional product offerings including Guardant RevealÔ for cancer recurrence and a simple blood test to screen for early signs of cancer.

In October 2020, Guardant Health initiated the Observation of ResiduAl Cancer with Liquid biopsy Evaluation (ORACLE) study, a 1,000-patient prospective, observational, multi-center study designed to evaluate the performance of its Guardant Reveal™ liquid biopsy test in early-stage cancer patients after the end of treatment to predict cancer recurrence across 11 solid tumor types.

The ORACLE study adds to currently underway clinical studies (COBRA, ACT-3, PEGASUS) that will support the expansion of the Guardant Reveal blood test from its first indication of early-stage colorectal cancer to multiple cancer types.

In October 2019, Guardant Health initiated the Evaluation of ctDNA LUNAR Assay In an Average Patient Screening Encounter (ECLIPSE) trial, a 10,000-patients prospective, multi-center registrational study to evaluate the performance of its LUNAR-2 blood test to detect colorectal cancer (CRC) in average-risk adults. If successful, Guardant expects data from the trial will support a premarket approval (PMA) submission to the FDA.

Tuba: Beyond NSCLC, what other indications can the Guardant360 test work for?

Kathryn Lang: The Guardant360 CDx test is the first FDA-approved liquid biopsy for comprehensive genomic profiling for all solid tumor cancers. Apart from lung, this includes the bladder, breast, cholangiocarcinoma, colorectal, endometrial, gastric and gastroesophageal, GIST, melanoma, ovarian, pancreatic, prostate, and thyroid indications.

Tuba: Do you believe the Guardant360 test will improve the quality of treatment for cancer patients?

Kathryn Lang: Comprehensive genomic profiling with liquid biopsy can help inform clinical decisions faster than with tissue biopsy because results from a liquid biopsy are accessible in under 7 days compared to an average of 21 days for results from a tissue biopsy. This time is crucial for patients with advanced-stage cancers as oncologists will be able to put their patients on the most appropriate first-line of treatment faster. If the Guardant360 test detects an actional biomarker, patients may be prescribed target therapies. Patients with targetable alterations experience higher response rates to targeted therapy vs. immunotherapy.

Tuba: What other tests have you developed for cancer patients?

Kathryn Lang: For patients across all stages of cancer, Guardant Health’s blood-based tests are increasingly helping to provide physicians with insights to personalize treatment plans and improve patient outcomes. For patients with advanced or metastatic cancer, the Guardant360 CDx performs complete genomic testing to identify potentially targetable biomarkers. This allows patients with advanced cancers to gain access to appropriate therapies or clinical trials to target the specific genes and proteins, also known as biomarkers, that are causing a person’s cancer cells to grow. Once treatment is started, Guardant360 Response monitors ctDNA levels to see whether a patient is responding to treatment or not and provides oncologists with the insights to consider whether to continue, stop, or explore other treatment options for their patients. For survivors of early-stage cancer, blood-based tests like Guardant Reveal look at circulating tumor DNA levels in a patient’s blood after surgery and help doctors consider whether to deploy a more aggressive treatment regimen, such as chemotherapy or immunotherapy, or continue to monitor the patient with tighter surveillance.

Blood-based tests are also being studied for their accuracy in detecting early signs of cancer in those who are asymptomatic and eligible for cancer screening. As part of its LUNAR Program, Guardant Health is currently evaluating a simple blood test to screen for early signs of colorectal cancer. The test is done via a simple blood draw that can occur in a doctor’s office or alternate settings by a trained phlebotomist and, therefore, has the potential to dramatically increase screening rates.

Source: Guardant Health

About Author: Kathryn Lang is the Vice President, Outcomes & Evidence at Guardant Health. Dr. Kathryn Lang is a board-certified hemato-oncologist, who completed clinical training in London, UK, and completed her Masters in Epidemiology at Erasmus MC, Rotterdam, and Bachelor of Medicine, Bachelor of Surgery (MBBS) from the Newcastle University. She is the lead of the clinical-genomics RWE outcomes research group at Guardant