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V.M. Raymond
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OA 12 - Emerging Genomic Targets (ID 679)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:H. Akita, Maurice Pérol
- Coordinates: 10/18/2017, 11:00 - 12:30, F203 + F204 (Annex Hall)
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OA 12.05 - Spectrum of 1,014 Somatic BRAF Alterations Detected in Cell-Free DNA of Patients with Advanced Non-Small Cell Lung Cancer (ID 9984)
11:00 - 12:30 | Author(s): V.M. Raymond
- Abstract
- Presentation
Background:
Somatic BRAF V600E is a National Comprehensive Cancer Network clinical therapeutic target in non-small cell lung cancer (NSCLC), occurring in 6% of tumors from patients with lung adenocarcinoma. However, approximately half of BRAF alterations are non-V600E that do not respond to FDA-approved vemurafenib or dabrafenib. Emerging evidence suggests some non-V600E mutations exhibit clinical response to novel therapeutic agents. We analyzed the landscape of BRAF mutations in a very large cohort of patients with NSCLC who underwent somatic genomic testing utilizing a CLIA-certified/CAP-accredited/NYSDOH-approved 73 gene cell-free circulating tumor DNA (cfDNA) panel which evaluates single nucleotide variants, and selected indels, fusions, and copy number amplifications.
Method:
The Guardant Health laboratory database was queried for cfDNA tests from patients with a diagnosis of NSCLC where a BRAF variant was identified. Literature was queried for a description of the known function of non-V600E BRAF mutations on serine-threonine kinase activity.
Result:
A total of 1,014 BRAF alterations were observed in 914 tests, with 234 unique alterations identified. The majority of variants were observed only once (75.6%; N=177). 43 alterations were synonymous and excluded from analysis. Plasma-detected BRAF amplification was the most common alteration, observed in 484 tests. Of the remaining variants, 33 of 190 had functional consequence reported in the literature (17.4%), 18 with gain of function or predicted gain of function, 13 with loss of function or predicted loss of function and 2 with no effect. BRAF V600E accounted for 51.1% of occurrences of variants with gain of function or predicted gain of function (N=95 occurrences). Recurrent (>10 occurrences) non-V600E gain of function mutations included G469A (13.4%; N=25 occurrences), K601E (8.0%: N = 15 occurrences), and N581S (7.0%; N=13 occurrences). Fourteen additional gain of function variants comprised the remaining 21% of occurrences. Recurrent loss of function BRAF mutations (>10 occurrences) included G466V and D594G.
Conclusion:
This is the largest reported cohort of somatic BRAF alterations in metastatic non-small cell lung cancer. Non-V600E alterations accounted for almost 50% of the gain of function variants. The spectrum of non-V600E alterations was consistent with reports from The Cancer Genome Atlas and prior published results from tissue genomic sequencing. The recurrent non-V600E variants identified in this cohort are emerging therapeutic targets with promising early clinical data. These findings advocate for more comprehensive BRAF genomic profiling and identification of patients eligible for clinical trials targeting these non-V600E classic mutations and demonstrate the ability of plasma-based cfDNA to detect these alterations.
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P1.11 - Patient Advocacy (ID 697)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Patient Advocacy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.11-004 - Impact of Liquid Biopsy on the Treatment of Low-Income Lung Cancer Patients (ID 8840)
09:30 - 16:00 | Author(s): V.M. Raymond
- Abstract
Background:
A number of patients with lung cancer receive their oncologic care at safety net hospitals that primarily treat low-income patients. These hospitals lack resources for rapid tissue biopsy and do not routinely offer liquid biopsies. Up to 25% of patients with non-small cell lung cancer (NSCLC) have insufficient tissue recovered on biopsy for genotyping. Guardant360 is a non-invasive cell-free circulating tumor DNA (cfDNA) test providing comprehensive genomic profiling of genes recommended by the National Comprehensive Cancer Network (NCCN).
Method:
We enacted a program at Los Angeles County-USC Medical Center aimed at increasing patient access to Guardant360. For testing costs, qualified patients were enrolled in the testing company's financial assistance program, subject to meeting financial eligibility criteria. Additionally, patients had access to a mobile phlebotomy service. We identified patients with metastatic NSCLC who had undergone Guardant360 testing between August 2016 and February 2017. Medical records were reviewed for results of molecular testing (tissue and cfDNA) and the impact of Guardant360 on clinical decision-making. We also reviewed tissue-based testing for EGFR mutations and ALK rearrangements ordered at Los Angeles County-USC Medical Center on 664 patients with lung cancer from 2005 to 2015.
Result:
Guardant360 testing was sent on 10 patients with NSCLC, 9 with adenocarcinoma and one with squamous histology. Seven had somatic mutations on cfDNA analysis with 3 of these seven patients having a targetable mutation, as defined by NCCN. Tissue was sent for molecular testing on 5 of the 10 patients with four patients having cfDNA results concordant with tissue results. For the remaining five patients, there was either insufficient tissue for testing (N=3) or testing was not ordered (N=2). In this cohort of uninformative tissue results, cfDNA results found one patient with an ALK rearrangement, one patient with a KRAS mutation, and no targetable mutations in three patients. The patient with ALK rearrangement had therapy changed based on Guardant360 results. On review of tissue-based testing for 664 patients, ordered at Los Angeles County-USC Medical Center, there were no ALK and EGFR testing results available for 79% and 75.8% of patients, respectively.
Conclusion:
Liquid-based biopsies can be useful in identifying patients with targetable mutations. Implementation of programs that give patients access to liquid biopsy in resource-limited environments, in which over 75% had incomplete tissue results, has the potential to impact care. This data highlights the potential benefit of liquid biopsy and illustrates how this program lead to changes in therapy for some patients.
