OncoCyte, a global oncology diagnostics company, recently announced that it will acquire Razor Genomics, which has developed a novel molecular diagnostic test for early-stage non-small cell lung cancer.
OncoCyte, a global oncology diagnostics company, recently announced that it will acquire Razor Genomics, which has developed a novel molecular diagnostic test for early-stage non-small cell lung cancer (NSCLC), the most common type of lung cancer.
According to the Centers for Disease Control and Prevention (CDC), cancer is the second leading cause of death in the United States (behind heart disease) and more people die from lung cancer than any other cancer. The 5-year relative survival rates for NSCLC range from 6-60%, depending on if the tumor has spread, according to the American Cancer Society. Cancer recurrence is the main culprit behind most NSCLC-related mortality. Despite being given the ‘all clear’ after getting surgery to remove cancerous lung masses, many early-stage NSCLC patients experience recurrence, indicating that they still had undetectable cancerous cells after complete resection.
“Over 30% of patients with surgically removed early stage lung cancer recur and over half of those that recur die within five years of surgery,” Ron Andrews, President and CEO of OncoCyte, said in the company’s press release.
OncoCyte aims to identify and clarify key unmet decision points to improve treatment and care for NSCLC patients. To do so, they are creating a continuum of molecular diagnostic testing for NSCLC, which is exactly why they were interested in Razor’s molecular test. This ‘treatment stratification test’ identifies high risk patients who could benefit from chemotherapy to eliminate the cancerous cells remaining after surgical resection. In addition, it identifies low risk patients who can more confidently decline chemotherapy because it predicts good outcomes post-surgery.
“In clinical studies, these patients demonstrated a significant improvement in survival rates following treatment,” Andrews told BioSpace. “Oncocyte is excited to add this molecular diagnostic test to their portfolio so lung cancer patients can better determine their best treatment options after surgical resection.”
Oncocyte is also developing a liquid biopsy to better determine if suspicious masses in the lung seen via computed tomography (CT) scan are cancerous and, therefore, if a lung biopsy is needed to confirm.
“It’s a marriage of two important end points that provide information for critical decisions within the lung cancer management continuum,” Andrews said about the acquisition. “Razor’s predictive decision point is directly adjacent to OncoCyte’s liquid biopsy detection decision point. After a positive liquid biopsy test, biopsy confirmation of cancer, and resection, a physician can order the treatment stratification test to help determine the next best steps for the patient. We can work with the same treatment team for both tests.”
Current treatment for non-small cell lung cancer
Patients, especially high-risk patients (such as smokers), receive low-dose CT scans to look for small masses called nodules, which could indicate the beginnings of cancer. Andrews said that about 1.5 million patients per year have these nodules, 550,000 of which are high-risk smokers. However, the CT scan is not specific, so doctors wouldn’t be sure if a mass was cancerous or not from just the scan – they need a biopsy to confirm. CT-guided lung biopsies carry some major risks, such as a collapsed lung (pneumothorax in up to 25% of biopsies) and bleeding in the lungs (pulmonary hemorrhage in up to 18% of biopsies), with an overall complication rate of up to 39% of biopsies. Not to mention that the mean cost of a lung biopsy is around $15,000.
Currently, the decision of whether or not to move forward with a biopsy is strictly based on the CT image and the doctor’s impression. Although there are risks of having the lung biopsy, the risk of delaying a potential cancer diagnosis could lead to poorer outcomes for the patient if they do have cancer, as catching and treating cancer in its early stages usually leads to better outcomes.
If a patient does have a biopsy and it confirms an early-stage lung cancer diagnosis, they typically undergo surgery to remove the cancerous masses in the lungs. However, surgery has its risks, such as a higher mortality rate compared with another type of radiation treatment (called stereotactic body radiotherapy, SBRT). A patient’s age is also closely tied to their outcomes, with patients over 70 having a greater difference in mortality rates between surgery and SBRT (most people diagnosed with NSCLC are over 65).
The doctors then determine whether the patient has a higher risk of the cancer returning and would benefit from additional chemotherapy or radiation. A patient could be considered higher risk for recurrence based on the size, location, stage of the cancer, and other factors, but it is tough to know who would benefit from chemotherapy or radiation after surgery.
A new vision for NSCLC treatment: OncoCyte’s liquid biopsy test for facilitating lung cancer diagnosis
The standard of care for NSCLC has a few obvious places for improvement, namely deciding whether a suspicious nodule on CT scan warrants the risk of biopsy and determining whether a patient needs additional chemotherapy or radiation after surgery based on their risk of recurrence within 5 years.
OncoCyte’s liquid biopsy test bridges the gap between CT scan and biopsy as a non-invasive test to help clinicians determine if a lung biopsy is needed to confirm a lung cancer diagnosis. While other liquid biopsies for most cancers focus on detecting tumor DNA in the blood, the tumors must be large enough to slough off enough DNA to be successfully detected in the blood. Instead of focusing on measuring markers directly from the tumor, this test focuses on measuring indirect markers via the patient’s immune response.
Using the patient’s blood sample, this test looks for a diagnostic gene expression signature in circulating immune cells that is correlated with the presence of cancer; an increase or decrease in the amount of RNA being produced by the body for certain types of immune cells indicates the presence of cancer. Different types of immune cells (such as T-cells, B-cells, eosinophils, basophils, neutrophils, etc.) each have their own unique RNA expression pattern that can be differentiated. This ‘immune repertoire RNA signature’ is thought to be one of the earliest detectable signals of cancer.
“The test can differentiate between T-cell and B-cell RNA signatures when they are activated against a specific tumor and underlying inflammation signals indicated by eosinophil, basophil, and neutrophil RNA signatures,” Andrews explained. “This gives us incredible sensitivity to understand the body’s very early stage immune response to cancer.”
To get the RNA, it is extracted from the patient’s blood sample and then undergoes next-generation RNA sequencing to figure out how much of each RNA sequence is present. A proprietary algorithm is used to correlate the resulting RNA expression information with known RNA signatures identified using OncoCyte’s biobank of 3,000 lung cancer blood samples with known patient outcomes (either benign or tumor nodules).
Ultimately, this test can help tell a patient if their nodules are benign and they do not need to move forward with a biopsy (they will just need to watch the nodules for any changes). If they receive a positive test, meaning they are at a higher risk of the nodules being cancerous, then they move forward with the biopsy to confirm.
Currently, this test is at the development stage and is working towards being CLIA-certified, which will allow OncoCyte to proceed with final clinical validation. They have already collected the patient blood samples needed for independent validation and will be able to correlate their test score with patient outcomes (for example, figuring out what percentage of patients with a positive test were confirmed to have cancer via biopsy). The clinical trial is estimated to be completed by mid-2020, pending CLIA certification.
Bridging the next gap in NSCLC care: Razor’s molecular treatment stratification test
Razor’s CLIA-certified molecular treatment stratification test bridges the gap between surgery and chemotherapy or radiation, which helps the doctor better understand the patient’s risk of recurrence within 5 years of surgery. Samples of resected tumor are processed, and the tumor RNA is analyzed for molecular markers that are correlated with having a low, medium, or high risk of recurrence. Patients with medium and high risk are recommended to begin chemotherapy after surgery to improve their outcomes.
In fact, in a study published in Journal of Thoracic Oncology in 2018, high-risk patients as determined by the test who received chemotherapy after surgery had a 5-year survival rate of 92% – a drastic improvement compared to the 49% 5-year survival rate of high-risk patients who did not undergo chemotherapy after surgery. The test was also more accurate in discriminating between low- and high-risk patients than the currently used guidelines for risk assessment from the National Comprehensive Cancer Network (NCCN). Tumor samples from 100 patients were analyzed to determine if they had low, medium, or high risk of recurrence within 5 years (52 low-risk and 48 medium- or high-risk 5-year mortality). Those at medium- or high-risk were given the option to pursue chemotherapy, 13 of which received chemotherapy.
While this study’s population is small, its impressive statistics prompted further study in almost 1,500 patients. Incorporating this test into the cancer staging system significantly improved the identification of high-risk patients and survival predictions compared to conventional staging without the test.
Moving forward, OncoCyte hopes to bring this test to market in the first quarter of 2020. The test was recently given a proposed ‘positive coverage decision’ from the Centers for Medicare and Medicaid Services (CMS), meaning it will be covered by Medicare. A final coverage decision will be issued within the next 6 months and will also determine how much the test will be reimbursed.
Other molecular diagnostic tests for NSCLC
While Razor’s treatment stratification test is the first of its kind for lung cancer, it mirrors the endpoint tested for by the Oncotype DX tests. Oncotype DX Breast Recurrence Score and Breast DCIS Score help determine if patients with certain types of breast cancer will benefit from chemotherapy after tumor resection and measure their risk of recurrence. The Colon Recurrence Score also measures the risk of recurrence in patients with certain stages of colon cancer who have had their tumors resected.
Biodesix is also developing a liquid biopsy, Nodify XL2, to determine the risk of lung modules being benign or cancerous, similar to OncoCyte’s liquid biopsy test. Although they report a 97% sensitivity (meaning 97% of patients with cancerous nodules are identified correctly) and a 98% negative predictive value (meaning 98% of all negative results are truly negative), the test has a low specificity (44%, meaning only 44% of patients with benign nodules are identified correctly) and their patient population is relatively small (178 patients). A low specificity means that there are many false positives, which means that people with benign nodules will still have to undergo biopsy to determine if their nodules are cancerous or benign.
Foundation Medicine offers a few clinically available tests to determine treatment options. FoundationOneLiquid is a liquid biopsy that measures circulating tumor DNA (ctDNA) given off by a solid tumor, including lung cancer, in a patient’s blood. It can help guide treatment decisions and clinical trial options for patients. However, it relies on the tumors being large enough to slough off enough ctDNA into the blood for detection and is therefore only indicated for advanced cancers. FoundationOneCDx is a companion diagnostic test on preserved tumor biopsy samples that can provide information about what therapies may work best based on the tumor’s genetic mutations and if a tumor could be resistant to any drugs. This requires a biopsy to be done to obtain a sample of tumor tissue and is also indicated only for the most advanced tumors that are large enough to shed ctDNA
Guardant Health offers the LUNAR assay for research use only. Their LUNAR-1 program is working to develop a test for accurately detecting residual cancer following resection surgery and risk of recurrence, similar to Razor’s treatment stratification test. They will initially focus on lung, breast, colorectal, and ovarian cancers. Their LUNAR-2 program is working to develop a screening test to detect cancer in asymptomatic patients, initially for colorectal cancer. Guardant also offers Guardant360, a ctDNA-based clinically available genomic profiling test to guide treatment options, similar to FoundationOne Liquid.
