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J.M. Hernandez Martinez
MA 12 - Circumventing EGFR Resistance (ID 665)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Wan Ling Tan, Nobuyuki Yamamoto
- Coordinates: 10/17/2017, 11:00 - 12:30, F205 + F206 (Annex Hall)
MA 12.10 - Clinical Utility of Plasma EGFR T790M Mutation Detection in Advanced Non-Small Cell Lung Cancer Patients According to RECIST Criteria (ID 9620)
11:00 - 12:30 | Author(s): J.M. Hernandez Martinez
Circulating tumor DNA (ctDNA) has emerged as a specific and sensitive blood based biomarker for detection of several mutations in non–small cell lung cancer (NSCLC). Other clinical applications for ctDNA include molecular assessment of patients at diagnosis and serial (real-time) monitoring of biomarker status or the development of resistance mutations.
Eighty patients with advanced NSCLC who either (Group 1) had a new diagnosis or (Group 2) had developed acquired resistance to an EGFR kinase inhibitor were analyzed with highly sensitive Biocept, Inc. TargetSelector[TM] Real Time PCR based plasma assays genotyping for the detection of EGFR mutations L858R, Del19 and T790M. In addition, group 1 was analyzed for KRAS, BRAF, ROS1 and ALK and circulating tumor cells (CTCs) before and after TKI treatment.
Our results showed concordance rates of EGFR, KRAS and ALK mutations for up to 90% between the tissue and blood samples in newly diagnosed patients (Group 1). Paired analysis of mutations status monitoring in this group (P= 0.016) showed that the pattern of mutant ctDNA and CTCs changed in response to systemic therapy in 83% of the cases (Partial response or disease progression; R2=0.808). Plasma ctDNA analysis of multiple mutations showed that 40% of patients had at least one more mutation besides the one detected in tissue biopsy; 28% of EGFR tissue positive patients also had a KRAS mutation. In addition, 75% of KRAS positive patients had a BRAF mutation. These results demonstrate that plasma ctDNA analysis may even detect mutations missed by standard tissue genotyping due to tissue heterogeneity. Plasma EGFR T790M mutation was analyzed in patients with clinical progression to TKI inhibitors. Considering the RECIST criteria, 58% of progressive disease, 10% of stable disease and 16% of partial response patients were positive for T790M. According to metastatic disease type (locoregional, oligometastatic, polimetastatic), the T790M mutation was found on 64.3% of polimetastatic patients, 30.8% of oligometastatic patients and 17.6% of loco-regional patients.
TargetSelector[TM] ctDNA assay is capable of rapidly detecting EGFR, KRAS and ALK mutations and is highly concordant with mutations present in tumor tissue with the robustness needed for real world testing to identify patients who progress on first line TKI therapy as well as for real-time monitoring of patients’ clinical status. Our findings highlight the importance of the RECIST criteria to define the progressive disease and determine the right moment to test for T790M mutation regardless the metastatic disease type.
P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
P1.07-040 - Prognosis-Relevant Subgroups in NSCLC According to Granulocytic Myeloid-Derived Suppressor Cell Frequency and Cytokine Levels (ID 9397)
09:30 - 16:00 | Author(s): J.M. Hernandez Martinez
The percentage of Polymorphonuclear-MDSCs (PMN-MDSCs) has emerged as an independent prognostic factor for survival in Non-small cell lung cancer (NSCLC) patients. Similarly, cytokine profiles have been used to identify subgroups of NSCLC patients with different clinical outcomes. This prospective study investigated whether the percentage of circulating PMN-MDSC, in conjunction with the levels of plasma cytokines, was more informative of disease progression than the analysis of either factor alone.
We analyzed the phenotypic and functional profile of peripheral blood T-cell subsets (CD3[+], CD3[+]CD4[+] and CD3[+]CD8[+]), neutrophils (CD66b[+]) and polymorphonuclear-MDSCs (PMN-MDSCs; CD66b[+]CD11b[+]CD15[+]CD14-) as well as the concentration of 14 plasma cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IL-27, IL-29, IL-31, and IL-33, TNF-α, IFN-γ) in 90 treatment-naïve NSCLC patients and 25 healthy subjects (HS).
In contrast to HS, NSCLC patients had a higher percentage of PMN-MDSCs and neutrophils (P<0.0001) but a lower percentage of CD3[+], CD3[+]CD4[+] and CD3[+]CD8[+] cells. PMN-MDSCs% negatively correlated with the levels of IL1-β, IL-2, IL-27 and IL-29. Two groups of patients were identified according to the percentage of circulating PMN-MDSCs. Patients with low PMN-MDSCs (≤8 %) had a better OS (22.045 months [95% CI: 4.335-739.735]) than patients with high PMN-MDSCs (9.265 months [95% CI: 0-18.810]). OS was significantly different among groups of patients stratified by both PMN-MDSC% and cytokine levels. Figure 1
Our findings provide evidence suggesting that PMN-MDSC% in conjunction with the levels IL-1β, IL-27, and IL-29 could be a useful strategy to identify groups of patients with potentially unfavorable prognoses.