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M. Wu
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MO16 - Prognostic and Predictive Biomarkers IV (ID 97)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:S. Toyooka, J.C. Yang
- Coordinates: 10/29/2013, 16:15 - 17:45, Parkside Auditorium, Level 1
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MO16.03 - Cytoplasmic ERβexpression predicts poorly efficacy and survival of EGFR-TKI in EGFR mutant NSCLC (ID 2563)
16:15 - 17:45 | Author(s): M. Wu
- Abstract
- Presentation
Background
Estrogen receptor pathway has been reported to be interacted with epidermal growth factor receptor (EGFR) signal pathway. This study focused on the impact of intracellular ERβ localization (cytoplasmic or nuclear) on the efficacy of EGFR-TKI.Methods
Tumor tissue specimens from 149 stage IV NSCLC patients treated with EGFR-TKI were analyzed using immunohistochemistry (IHC) for ER expression (ERαorβ) and their associations with clinicopathological variables and clinical outcomes. Significance of cyto-ERβ expression was further examined in NSCLC cell lines.Results
The expression of ERα and ERβ was detected in 15% and 28.9% of the patients, respectively. Cyto-ERβ positive cases showed shortened progression free survival (PFS) compared with cyto- ERβ negative ones (3.1 months vs. 7.3 months, p=0.061). In the subgroup with concurrent EGFR mutation, the differences of PFS were enlarged with significant statistics (4.7 months vs. 10.9 months, p=0.042). COX’s proportional hazard model showed that female, EGFR mutation and c- ERβ negative expression were independent predictive factors for PFS. PC-9 cells present ERβ in cytoplasma as well as nucleus. Estrodial (E2) induced PC-9 cells moderately resistant to erlotinib with a 3-fold increase of IC50, and the resistance can be reversed by ER blocker (fulvestrant) or siRNA directed to ESR2. The function of E2 was accomplished by nongenomic activation (MAPK phosphorylation) caused by E2 via cyto- ERβ. Combination therapy with erlotinib and fulvestrant turned out to be far more effective than either treatment alone in PC-9 cells. Furthermore, 2 patients harboring both EGFR mutation and cyto-ERβ expression underwent PD of EGFR-TKIs, and re-obtained disease control after receiving combined EGFR-TKIs with fulvestrant.Conclusion
Cyto-ERβ expression may predict relatively poor efficacy to EGFR-TKI compared with non- cyto-ERβ expression in NSCLC patients harboring EGFR mutation.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MO21 - Prognostic and Predictive Biomarkers V - EGFR (ID 98)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:D.C. Lam, S.M. Lee
- Coordinates: 10/30/2013, 10:30 - 12:00, Bayside Auditorium A, Level 1
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MO21.09 - Dynamic, quantitative, and non-invasive analysis ofT790M mutation in matched plasma DNA from pre-and post-EGFR-TKI treatment for advanced non-small cell lung cancer (ID 2568)
10:30 - 12:00 | Author(s): M. Wu
- Abstract
- Presentation
Background
Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer patients (NSCLC) is attributed to the T790M mutation of EGFR. Here, we evaluated T790M mutation using dynamic, quantitative and non-invasive method and explored its role predicting outcomes of EGFR-TKI treatment.Methods
We enrolled 135 EGFR-TKI-resistant NSCLC patients in the study. Pre- and post-EGFR-TKI treatment (pre-TKI and post-TKI, respectively) plasma samples were obtained for analysis. T790M mutation was measured qualitatively and quantitatively by the amplification refractory mutation system (ARMS) and digital polymerase chain reaction (D-PCR).Results
D-PCR was more sensitive than ARMS in detecting the T790M mutation (pre-TKI: 29.4% (32/109) vs 5.5% (6/109), P<0.001; post-TKI: 43.0% (58/135) vs 25.2% (34/135), P=0.001). Patients with a pre-TKI T790M mutation (N=32) showed shorter progression free survival (PFS) and overall survival (OS) than patients without a T790M mutation (N=77) (9.2 vs 12.7 months, P=0.004; and 19.3 vs 31.9 months, P=0.001, respectively). No differences were observed in post-TKIPFS or OS (12.5 vs 12.2 months, P=0.744; and 27.0 vs 29.7 months, P=0.636, respectively). Post-treatment patients were divided into high-frequency (>4.375%) and low-frequency (≤4.375%) groups, according to the mutant T790M-to-wild-type gene ratio calculated from D-PCR results. Patients in the high-frequency group showed a significantly shorter OS than the low-frequency group (20.67 vs 29.13 months, P=0.009).Conclusion
D-PCR is more sensitive than ARMS in detecting the T790M mutation. The presence of a pre-TKI T790M mutation and a high frequency of post-TKI T790M mutation predicted poor outcomes of EGFR-TKI treatment.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
