New prospective data on DetermaRx™, a 14-gene molecular treatment stratification test developped by Oncocyte, a molecular diagnostics company, that identifies stage I-IIA non-small cell lung cancer (NSCLC) patients at high-risk of recurrence despite curative surgery who may benefit from the addition of chemotherapy, will be presented by Gavitt Woodard, M.D., Assistant Professor, Yale School of Medicine at the IASLC 2020 North America Conference on Lung Cancer, hosted by the International Association for the Study of Lung Cancer.

Gavitt Woodard, M.D., a thoracic surgeon and assistant professor at Yale University. She received her medical degree from Stanford University and completed her general surgery residency and cardiothoracic surgery fellowship at UCSF. Woodard is the recipient of an American Association of Thoracic Surgeons Robotics Fellowship Award as well as a Chief Resident Achievement Award from UCSF. Her research focuses on the genetic drivers of early-stage lung adenocarcinoma, the role of systems genetics in cancer development, small molecule drug development and preclinical testing of novel therapeutics. Photo courtesy: © 2020 Oncocyte. Used with permission.

The test, which has been validated in two independent cohorts with close to 1400 patients and outperformed National Comprehensive Cancer Network (NCCN) criteria in identifying patients at high risk for mortality from stage IA, IB, and IIA non-squamous NSCLC, is reimbursed by Medicare and has seen rapid adoption in its first year of launch across seventy hospitals, including  (NCCN) and National Cancer Institute (NCI) cancer centers.

The presentation during the IASLC 2020 meeting will highlights results from the prospective study of 250 consecutive stage I-IIA non-squamous NSCLC patients who received the DetermaRx test. This included patients with high-risk status as identified by the DetermaRx where test was used to inform the use of adjuvant chemotherapy. Noteworthy, 94% of patients who selected adjuvant chemotherapy were cancer-free after five years of follow-up. In contrast, one in three high-risk patients who elected to forego chemotherapy had a recurrence.

The presentation also include data from low-risk patients identified by the DetermaRx test who were not treated with chemotherapy. The data demonstrated that only 5% of these patients reported a cancer recurrence, suggesting that this test may also inform the choice to avoid potentially unnecessary but toxic chemotherapy.

The data expand and reinforce the strong survival benefit previously demonstrated in the first 100 patient study previously published.

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EGFR and Lung cancer
A total of 1 in 3 patients with metastatic lung adenocarcinoma has an actionable mutation, like EGFR, a genetic alteration that drives the growth and spread of metastatic NSCLC and can be targeted with therapy specific to the mutation.

The epithelial growth factor receptor (EGFR), a member of the HER family of tyrosine kinase receptors and is expressed in more than half of all NSCLC, has been recognised as a target oncogenic driver to detect lung cancer in a subset of patient. And patients should me tested regardless of smoking status, gender, race or age.[1][2][3][4]

However, DetermaRx identified high-risk patients who responded to adjuvant chemotherapy, independent of EGFR status and in evaluating data in a cohort of 150 patients, the EGFR status was not prognostic.

Aduara trial
Data from the ADUARA trial, presented at the annual meeting of the virtual meeting of the  American Society of Clinical Oncology (ASCO) Annual Meeting held 29-31 May 2020, reported improved survival rates in surgically resected NSCLC patients with an EGFR mutation treated with the targeted therapy osimertinib (Tagrisso®; AstraZeneca) [5][6]

Osimertinib is a third-generation, irreversible EGFR TKI designed to inhibit EGFR sensitizing mutations—exon 19 del and L858R mutations, inhibit mutated EGFR with the T790M resistance mutation and have lower activity against wild-type EGFR.

The phase III trial demonstrated a statistically significant and clinically meaningful benefit for adjuvant osimertinib in patients with stage IB, II, or IIIA EGFR-mutant non-small cell lung cancer (NSCLC) with complete tumor resection.

These results inform the usage of the targeted therapy osimertinib in conjunction with chemotherapy, in EGFR positive patients.

“We are very pleased that the initial data showing this test’s impact on cancer recurrence was maintained in the 250-patient expanded data set. This result establishes DetermaRx as the post- surgical treatment standard for patients diagnosed with NSCLC,” said Edgardo S. Santos, M.D., Florida Precision Oncology, a Division of Genesis Care and an early adopter of the test.

“The integration of testing for targeted therapy, including EGFR mutation status and chemotherapy selection by DetermaRx on the same sample, will enable oncologists to optimize and sequence treatment post-surgery. In my opinion, these two tests together close the few remaining gaps that we currently face in deciding adjuvant therapy for early-stage adenocarcinoma of the lung. With these results, I would feel confident initiating chemotherapy, followed by targeted therapy for the EGFR-positive, DetermaRx high-risk patients I see in my practice.”

Key takeaways

  • Combining DetermaRx risk status with EGFR mutation status may help inform optimal treatment strategies for non-small cell lung cancer (NSCLC) patients who are EGFR- mutation-positive.
  • DetermaRx may inform the usage of chemotherapy, in addition to osimertinib, in the approximately 33% of EGFR positive patients who DetermaRx also identified as high-risk for cancer recurrence.
  • Given these data, Oncocyte will be offering EGFR mutation testing and DetermaRx on the same sample starting this quarter.

“Coming off a very strong third quarter, during which we received final Medicare pricing within our expected range, and saw DetermaRx order volumes more than double from the second quarter, we are extremely excited about the release of the new prospective data” said Padma Sundar, Senior Vice President, Commercial at Oncocyte.

“We believe these data expand the utility of DetermaRx for both chemotherapy and targeted therapy selection, ultimately facilitating continued rapid market adoption. As DetermaRx is the only validated test for guiding standard of care adjuvant chemotherapy post-surgery, we will continue to add other actionable markers to our testing as more therapy options become available for these patients. The addition of EGFR testing for osimertinib is an exciting first step in that direction,” she added.

Key Opinion Leader Webinar
In addition presentations during the IASLC 2020 meeting, a KOL webinar will be presented on October 22nd at 11:00 am (Pacific Time) by Gavitt Woodard, M.D., Assistant Professor, Yale School of Medicine, cardiothoracic surgeon and lead author on the study, and David Gandara, M.D., Professor of Medicine Emeritus at the University of California, Davis, and Director of Thoracic Oncology at the UC Davis Comprehensive Cancer Center (UCDCCC). For more details on the webinar and to register, please click here.

Other deveopments
Oncocyte is also developing DetermaIO™, a gene expression test that identifies patients more likely to respond to checkpoint inhibitor and other immunotherapies. To strengthen Oncocyte’s immune therapy diagnostic offering, the company also announced plans to commercialize Therasure-CNI, a tumor naïve blood based test licensed from Chronix Bioscience, which has shown effectiveness at monitoring the efficacy of immune therapy.

Clinical trials
AZD9291 Versus Placebo in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy. (ADAURA) – NCT02511106

Highlights of Prescribing Information
Osimertinib (Tagrisso®; AstraZeneca) [Prescribing Information]

[1] Sholl L, Aisner D, Varella-Garcia M, et al. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777.
[2] Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846. doi:10.1038/ncomms5846.
[3] Bergethon K, Shaw A, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30:863-870.
[4] Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12:175-80.
[5] Herbst RS, et al. Phase III study assessing the efficacy of adjuvant use of targeted agent osimertinib in patients with localized non-small-cell lung cancer and EGFRmutation after complete tumor resection and adjuvant chemotherapy. ASCO Virtual Meeting, 29-31 May 2020, Abstract
[2] Soria JC, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113‐125. [Article]

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