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Chong-Jen Yu
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OA11 - Decomplexifying Molecular Targets, Immunotherapy and Treatment Settings in the Real World (ID 137)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:Kumar Prabhash, Jyoti D Patel
- Coordinates: 9/09/2019, 14:00 - 15:30, Interlaken (1988)
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OA11.01 - Complex EGFR Mutations in Lung Adenocarcinoma (Now Available) (ID 2114)
14:00 - 15:30 | Author(s): Chong-Jen Yu
- Abstract
- Presentation
Background
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) provides a favorable treatment efficacy for EGFR-mutant lung cancer patients. Majority of EGFR mutations are a single mutation, including deletion in exon 19 (del-19) or L858R in exon 21. There is a subset of patients with complex EGFR mutations which contains two or more EGFR mutation types. It is unclear the treatment efficacy to different EGFR TKIs and survival prognosis for the complex EGFR-mutant patients due to small sample sizes of the prior studies. This study aimed to improve the understanding of the clinical characteristics and the prognosis of EGFR TKI treatment in lung adenocarcinoma patients with complex EGFR mutations.
Method
Between June 2005 to July 2018, patients harboring lung adenocarcinoma with complex EGFR mutations who were treated with EGFR TKIs were collected for EGFR mutation analysis by direct Sanger sequencing. Patients’ clinical characteristics, EGFR mutation status, treatment response, progression-free survival (PFS) and overall survival (OS) were analyzed. Patients harboring tumor with de novo T790M mutations were excluded for evaluation of EGFR TKI effectiveness.
Result
There were 175 patients (6.3%) with complex EGFR mutation from 2390 EGFR-mutant patients. Of the 175 complex EGFR-mutant patients, 122 patients who received EGFR TKIs were enrolled for evaluation of TKI effectiveness. Patients with the classical mutation pattern (del-19 or L858R) had higher treatment response rate (78.6% vs. 47.4%; p = 0.001) and PFS (8.6 months vs. 3.3 months; p = 0.006) than those without the classical mutations patterns (Fig-A). In multivariate analysis, female (p = 0.002), patients with disease relapse status, and the classical mutation patterns (p < 0.001) were associated with prolonged PFS. Compared with gefitinib and erlotinib, afatinib had a longer PFS, especially for patients without the classical mutation patterns. For OS, multivariate analysis revealed that female (p < 0.001), patients harbored classical mutation pattern (p = 0.001) (Fig-B), and patients with disease relapse status had longer OS. There were 51 patients who had re-biopsy tissue samples after acquired resistance to EGFR TKIs, 17 (33.3%) samples harbored T790M. In addition, small cell lung cancer transformation was detected in 3 (2%) patient’s re-biopsy tissue samples.
Conclusion
Female patients with complex EGFR-mutant lung adenocarcinoma and the classical mutation patterns have higher response rate, longer PFS and OS than those without the classical mutation patterns. Afatinib was active in lung adenocarcinoma harboring complex EGFR mutations, and may especially benefit patients without the classical mutation patterns due to longer PFS results.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-39 - Serial Plasma ctDNA Tests Identify Genomic Alterations for Early Prediction of Osimertinib Treatment Outcome in T790M+ NSCLC (ID 2396)
10:15 - 18:15 | Author(s): Chong-Jen Yu
- Abstract
Background
Recent advances in detection of genomic DNA from plasma samples allow us to follow the alteration of shedding tumor DNA in plasma before and after systemic treatment with multiple biopsies. Osimertinib is the standard of care for NSCLC patients with T790M mutations. We plan to use serial plasma cfDNA genomic alteration to predict osimertinib efficacy and search for possible resistance mechanisms.
Method
We prospectively collected plasma from patients of EGFR mutation-positive NSCLC who harbored acquired EGFR T790M mutation following prior EGFR-TKI therapy. Plasma samples were collected before starting osimertinib treatment, 4 weeks following osimertinib treatment and upon disease progression. ctDNA were detected by Guardant360 gene panel test.
Result
Fifteen patients (median age 62 [range 48-77], 53% men, 53% exon 19 deletion and 47% exon 21 L858R mutation) received osimertinib treatment. Acquired T790M mutation was diagnosed by using plasma sample only (Cobas® or digital PCR) (n = 11), tissue or pleural effusion only (n = 2), and both tissue and plasma samples (n = 2). Before starting osimertinib treatment, activating mutations were detected in plasma in all patients, T790M was detected in 93% (n = 14) and TP53 mutation was detected in 47% (n = 7) of the patients by using Guardant360. After osimertinib treatment, 11 out of the 14 patients had non-detectable plasma T790M at the 4th week. Follow-up CT at least 8 weeks following osimertinib treatment of the 11 patients disclosed decreased tumor size (6 confirmed PR, 1 unconfirmed PR and 5 SD by RECIST criteria). The remaining 3 patients who had detectable plasma T790M (n = 2) or increased activating mutation allele frequency (n = 1) at the 4th week had progressive disease within 16 weeks. The first patient had initial PR but later developed C797S on progression. The second patient developed new liver tumor following prior stable disease. This patient had baseline TP53 and CDKN2A mutations detected in the plasma, and allele frequencies decreased at the 4th week and increased on progression. The last patient had rapid progression on osimertinib treatment, and alterations in PTEN and TP53 were detected on baseline and increased at the 4th week and on progression. In that patient, T790M mutation was not detectable at the 4th week but activating mutation increased in allele frequency at the 4th week and on progression. Regarding patients with baseline TP53 mutation, 4 (57%) patients who had non-detectable plasma TP53 mutation at the 4th week achieved disease control, and 2 (29%) patients had detectable or increased TP53 mutation allele frequency had PD within 16 weeks.
Conclusion
4 week plasma ctDNA following osimertinib treatment may predict early progression within 16 weeks.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-34 - FCGR2B Expression as a Regulator of Immunity in Non-Small Cell Lung Cancer Patients (Now Available) (ID 458)
10:15 - 18:15 | Author(s): Chong-Jen Yu
- Abstract
Background
FCGR2B (CD32B), a receptor on the B cell membrane, induces the production of inhibitory messages to maintain the homeostasis of the immune system and prevent excessive activation of B cells to attack their own antigens. Therefore, FCGR2B may cause immune cells to not effectively search and kill for cancer cells.This study examined the level of FCGR2B expression on B cells associated with immunity in non-small cell lung cancer (NSCLC) patients.
Method
Healthy volunteers and lung cancer patients were recruited. All control donors’ and patients’ peripheral blood were collected. 200ul blood with appropriate amount of antibody was incubated for 10-15 min at room temperature in the dark and then lysed with 1ml VersaLyse Lysing Solution for 10-15 min at room temperature in the dark. Resuspend in 1ml PBS+ 1% fix solution then were counted by cytoflex flow cytometer (Beckman Coulter). For surface marker analysis, B cells were collected assessing the levels of CD19, CD32, CD21, CD24, CD27, CD38, and IgM/IgD by flow cytometric assay. T cells subtypes including CD3, CD4, CD8, CD27, CD28, CD45, CD45RA, CD57, CCR7 and PD1 were counted by cytoflex flow cytometer.
Result
In this study, healthy volunteers (n=9 ) were compared with NSCLC patients (n=17) to detect the expression of FCGR2B on B cell. We found that Class Switched Memory Cell in NSCLC patients had lower performance than healthy subjects (NSCLC patients v.s. healthy subjects: 65.10 ± 15.72 v.s. 70.76 ± 7.26, p = 0.013). Class Switched Memory Cell was significant lower in advanced stage than that in early stage NSCLC patients (advanced stage v.s. early stage: 54.68 ± 27.21 v.s. 77.73 ± 7.12, p = 0.044). The expression of FCGR2B (CD19CD32) in NSCLC patients was slightly lower than that in healthy subjects (NSCLC patients v.s. healthy subjects: 19.68 ± 10.07 v.s. 32.98 ± 23.92, p = 0.099), but did not reach statistically significant differences. The expression of FCGR2B (CD19CD32) was significantly positively correlated with CD4 Naïve T cell ( R = 0.789; B = 0.291; p < 0.001) and CD3CD4CD45RA (R = 0.765; B = 0.301; p = 0.001).
Conclusion
NSCLC patients with reduced numbers of Class Switched Memory B Cell are more prone to progress lung cancer disease. The positive correlation between FCGR2 B cells and naive T cells in blood is also observed. Future studies focusing on the presence of these B cell subtypes, antigen specificity and interaction with T cells are necessary to further elucidate in NSCLC patients.
