GENOMIC TESTING

In an interview with Targeted Oncology during the 2020 Association for Molecular Pathology Annual Meeting, Ozge Ceyhan-Birsoy, PhD, discussed genetic testing methods for patients with hereditary predisposition and the molecular research underway at MSKCC to improve testing in this patient population.

The Access to Comprehensive Genomic Profiling Coalition has been formed by 7 leading diagnostic companies and laboratory providers across the United States to advocate for appropriate broad health insurance coverage of comprehensive genomic profiling for patients with advanced-stage cancer.

A pathogenic germline mutation rate of about 5% has been identified in women who had a family history of breast or ovarian cancer but no personal history of either disease.

In an interview with Targeted Oncology, Carl Morrison, MD, DVM, senior vice president Roswell Park Comprehensive Cancer Center, discussed the rationale for evaluating the Ion Torrent-based approach to predicting response to immunotherapy. He highlighted the importance of this in the clinical setting and advances are necessary to further validate this as a biomarker of response.

Microsatellite instability has been an FDA-indicated biomarker for immunotherapy since 2017, when the PD-1 inhibitor pembrolizumab was approved for patients with solid tumors found to be mismatch repair deficient or MSI high. Other approvals since then, such as for the combination of ipilimumab and nivolumab in patients with MSI-H/dMMR metastatic colorectal can­cer, have established the relevance of cancer thera­pies for tumors with this biomarker specifically rather than tumor histology alone.

In an interview with Targeted Oncology, Whitney Ducaine, MGC, CGC, CN-BM, discussed the evolution of genetic testing in oncology. She highlighted the importance of having conversations with genetic counselors to help inform the patient on their familial risks as well to help inform treatment decisions.

High volumes of mutations observed through liquid biopsies may be associated with an improvement in progression-free survival  and clinical benefit after first-line standard-of-care pembrolizumab-based therapy in patients with metastatic non-small cell lung cancer, according to findings from a prospective biomarker trial conducted by investigators at the University of Pennsylvania Perelman School of Medicine and Abramson Cancer Center, which were published in Clinical Cancer Research.

Treatment with immune checkpoint inhibitors appears to elicit limited clinical activity in patients with osteosarcoma. In a study, investigators at MD Anderson Cancer Center found that certain factors like poor infiltration of the tumor by immune cells, low activity from available T cells, a lack of immune-stimulating neoantigens, and multiple immune-suppressing pathways may interfere with response to immunotherapy in these patients, according to a press release from the organization.<br /> &nbsp;

Next-generation sequencing in patients with chronic lymphocytic leukemia treated with the combination of chlorambucil and ofatumumab showed that the presence of&nbsp;TP53,&nbsp;SF3B1,&nbsp;and&nbsp;NOTCH1&nbsp;mutations were predictive of reduced efficacy, according to the results of the phase III COMPLEMENT1 trial published in&nbsp;Haematologica.

The Ion Torrent Oncomine Myeloid Research Assay, the first fully-integrated next-generation sequencing platform, will be available in 2020 on the new Ion Torrent Genexus System for research use, according to a press release from Thermo Fisher Scientific. The platform features automated workflow to allow for result delivery within a single day, requiring minimal user intervention and tissue sample input.

MI Genomic Profiling Similarity Score, the latest addition to the comprehensive genomic profiling armamentarium at Caris Life Sciences, has been launched, according to a press release from the company

The FDA granted an Investigational Device Exemption approval to the Personal Genome Diagnostics Inc. elio^TM&nbsp;tissue complete assay for use in a Merck trial evaluating pembrolizumab combinations in non&ndash;small cell lung cancer, according to a press release from PGDx, developer of the assay.

A plethora of new technology has been developed to assist in identifying targetable mutations, including next- generation sequencing. NGS assays that identify tumor genes can range in use from targeted to comprehensive panels, all of which have accelerated the advancement of personalized medicine.

Precision medicine has afforded oncologists the opportunity to develop individualized approaches to treat non&ndash;small cell lung cancer, one of the most devastating malignant disorders, which until the past decade was thought to be invariably fatal within months.

In an interview with&nbsp;Targeted Oncology, Willemina R. Geurts-Giele, PhD, discussed the accuracy of detecting&nbsp;MET&nbsp;exon 14 skipping mutations in patients with NSCLC with DNA-based NGS panels. These findings were presented at The Association for Molecular Pathology Annual Meeting and Expo.

The emergence of resistance mutations in patients with cancer who receive targeted therapies is an expected development that will require new diagnostic methods of identifying the mechanisms through which these alterations occur, according to Fei Dong, MD, during the 2019 Association for Molecular Pathology Annual Meeting.<br /> &nbsp;

In a presentation describing the utility of circulating tumor DNA liquid biopsy assays at the 14th Annual New York Lung Cancers Symposium, Bob T. Li, MD, MPH, said that plasma genotyping demsonstrates practice-changing potential in non&ndash;small cell lung cancer.

Testing for driver mutations is essential before initiating therapy in patients with non&ndash;small cell lung cancer, because there is a risk that the type of upfront treatment chosen could add to the toxicity of, and spur resistance to, targeted therapy options, Suresh S. Ramalingam, MD, said at the 14th Annual New York Lung Cancers Symposium.

At the 2019 Association for Molecular Pathology Annual Meeting and Expo, Adam Fisch, MD, PhD, presented a unique patient case where a patient with acute myeloid leukemia harboring a <em>FLT3</em>-TKD mutation lost the mutation following relapse on gilteritinib.<br /> &nbsp;

Yuma Regional Medical Center Cancer Center has implemented a genetic cancer screening and testing for their patients through collaboration with Myriad Genetics, a molecular diagnostic testing company, according to a presentation by Erica Martinez, RN, OCN, at the Association of Community Cancer Centers&rsquo; 2019 National Oncology Conference. After partnering with Myriad Genetics, the cancer center saw a 4-fold increase in genetic testing of patients with cancer in the first 4 months, which led to a change in clinical management in 20% of those cases.

In an interview with&nbsp;Targeted Oncology, Raoul S. Concepcion, MD, discussed the existing challenges with implementing genetic testing and genetic counseling in community practices and how they can potentially be addressed.

Among patients with acute myeloid leukemia and myelodysplastic syndrome who completed myeloablative allogeneic hematopoietic stem cell transplantation, the predictive utility of testing circulating tumor DNA was comparable with that of mutation persistence evaluation in matched bone marrow samples, according to a study published recently in Blood.

In a presentation at the 2019 ESMO Congress on a case series of 7 pretreated patients with <em>NRG1</em>-positive tumors, Stephen Liu, MD, and colleagues discussed the efficacy of afatinib and explained that afatinib may be a potential treatment option for <em>NRG1</em>-positive tumors across multiple cancer types.

Findings from an interim analysis of the National Lung Matrix Trial, a large, multiarm trial involving patients with non&ndash;small cell lung cancer, demonstrated both promising activity and shortcomings in predefined goals in a presentation at the 2019 World Conference on Lung Cancer.

At the recent <em>20th Annual </em>International Lung Cancer Congress&reg; in Huntington Beach, California, a number of very prominent contributors to the lung cancer translational and clinical field provided updates regarding novel strategies to address unmet needs.

Multiple presentations at the 2019 ESMO Congress add to the evidence that blood-based biomarkers have predictive utility in advanced non-small cell lung cancer. Blood-based next-generation sequencing has also shown clinical utility in aiding treatment decisions for physicians treating this disease.

In an interview with&nbsp;<em>Targeted Oncology</em>, Gregory Gores, MD explained the role of molecular therapy and the use of genetic testing to guide treatment of iCCA.

Gulam A. Manji, MD, PhD, discusses the need to identify mutations that may be actionable in patients with colorectal cancer. The identification of such mutations can further impact patient survival and improve efficacy, says Manji, in both CRC and other gastrointestinal cancers.

In an interview with <em>Targeted Oncology</em>, Dean A. Fennell, MD, PhD, explained the need for the MIST trial and personalized treatment for patients with mesothelioma.

Advances in molecular profiling have driven development and use of personalized medicine approaches in oncology, enabling detection of biomarkers for predicting prognosis and treatment response and determining inheritable cancer risk.