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Terry L Ng
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-29 - Disrupting the Paradigm: Partnering with Oncogene-Focused Patient Groups to Propel Research (ID 1498)
09:45 - 18:00 | Author(s): Terry L Ng
- Abstract
Background
Genomic alterations drive more than 60% of adenocarcinoma cases of non-small cell lung cancer (NSCLC). About 20% of cases will have an oncogenic driver (EGFR, ALK, ROS1, BRAF, NTRK, etc.) that can be treated with approved targeted therapy drugs, and more (RET, Exon 20 insertions, etc.) have clinical trial options. Patients and caregivers dealing with these cancers have organized globally into oncogene-focused groups (“Groups”—see Table 1) and are building partnerships that seek to provide support, increase awareness and education, accelerate and fund research, and improve access to effective diagnosis and treatment.
Method
We partnered in a variety of ways to accelerate research. While each Group sets its own research priorities, we’ve found successful collaborative research has the following seven characteristics. It includes patients from the start, in all aspects of the project. It addresses questions meaningful to patients. It develops patient-centered measurements. It accommodates patients’ clinical realities. It leverages social media and patient groups. It shares progress with participants frequently. It makes results rapidly and freely available.
Result
These methods have enabled the Groups to collaborate successfully with clinicians, researchers, advocacy organizations, and industry to generate ideas for next steps in research for their disease, forge new studies and clinical trials for a specific oncogenic driver, create new patient-derived models of oncogene-driven cancers to study acquired resistance, develop registry-based studies to collect real-world data, and guide patients to clinical trials.
Conclusion
Oncogene-focused patient-caregiver groups are creating new paradigms across the research continuum. They have demonstrated that their partnerships with advocacy organizations, clinicians, researchers, and industry, can increase available patient-derived models, patient data, and specimens among geographically distributed, oncogene-driven cancer populations.
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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-06 - Detection of ctDNA and Correlation with Tumor Mutation Testing in Early Stage NSCLC (ID 2950)
10:15 - 18:15 | Author(s): Terry L Ng
- Abstract
Background
In advanced disease, circulating tumor (ctDNA) has proven a viable alternative to tissue based molecular testing to identify patients with lung adenocarcinoma (LUAD) eligible for targeted therapies. ctDNA is under investigation for utility in early cancer detection and non-invasive companion diagnostics to allow for identification of targetable biomarkers in patients who may benefit from neoadjuvant targeted therapy. However, in the early stage cancer setting, ctDNA has been limited by reliance on interrogation of genomic alterations alone resulting in low detection rates (13% stage I, 22% stage II, 40% stage III, Abbosh et al, Nature 2017). Herein, we test the ability of the novel ctDNA-based assay to detect ctDNA in patients with early stage LUAD, and secondarily, to identify targetable oncogenes in these patients.
Method
Eligible patients had stage IA-IIIA LUAD deemed surgically resectable. Following consent, plasma samples were collected prior to surgery or neoadjuvant therapy. Circulating free DNA (cfDNA) was analyzed for ctDNA with the LUNAR assay (Guardant Health), which utilizes an integrated genomic and epigenomic ctDNA assessment at a tumor allelic fraction down to 0.01% to report “ctDNA detected” or “ctDNA not detected”. This single blood sample cfDNA assay utilizes a variant filter to distinguish tumor from non-tumor derived cfDNA alterations in the absence of other genomic DNA (e.g. tissue sequencing or peripheral blood mononuclear cells). Molecular analysis of paired FFPE primary tumor specimens was performed using the Illumina TruSight Tumor 26 or ArcherDx VariantPlex Solid Tumor library preparation kits followed by next-generation sequencing (NGS) on the Illumina platform in a CLIA-certified laboratory. Sensitivity for tumor driver mutation detection is evaluated by comparing tumor drivers identified in ctDNA with those identified in corresponding paired primary tumor specimens.
Result
We enrolled 31 patients with early stage LUAD who ultimately underwent surgical resection, 29 of whom completed LUNAR testing (19 with stage I, 4 with stage II and 6 with stage IIIA). Analysis of tumor tissue identified a driver mutation in 83% (24/29) of cases (KRAS=11, EGFR=10, MET=3, ALK=1). A genomic cancer-associated mutation was identified in 16%, 25% and 67% in stage I, II, and III, respectively. The LUNAR assay demonstrated 100% specificity for EGFR and KRAS mutations. The incorporation of the epigenomic classifier enhanced pre-operative ctDNA detection to 26% of Stage I, 50% of stage II, and 67% of stage III patients.
Conclusion
The majority of patients with early stage LUAD had an identifiable oncogene alteration, consistent with data from advanced disease. Utilizing a plasma only, integrated genomic and epigenomic ctDNA assay demonstrated improved performance over tumor informed approaches. The ctDNA detection rate increased with disease stage, consistent with increased tumor burden. With 100% tissue concordance of EGFR and KRAS alterations identified in ctDNA, ctDNA may prove an option for not only identification of early stage LUAD, but also identifying biomarker positive LUAD eligible for clinical trials utilizing targeted therapy in the neoadjuvant setting.
