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Xueqin Chen
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-046 - The Feasibility of Osimertinib Treatment on Brain Metastases in NSCLC Patients After 1<sup>st</sup> Generation EGFR-TKI Resistance: A Preliminary Study (ID 8588)
09:30 - 16:00 | Author(s): Xueqin Chen
- Abstract
Background:
NSCLC patients with activating EGFR mutations benefit from 1[st] generation EGFR-TKIs. It eventually develops acquire resistance after 10-12 months during of response. Of note, approximately one-third of those patients develop brain metastases, which deteriorate their quality of life and survival. Few effective therapeutic options are currently available for BM patients. Several case studies have showed the well response with osimertinib in BM patients. BM model also found the high penetration rate of Osimertinib into blood-brain barrier. This study evaluated the feasibility of osimertinib treatment on BM patients after 1st generation EGFR-TKI resistance.
Method:
Patients with advanced or recurrent NSCLC who had progressed during EGFR-TKIs treatment were collected from our previous clinical trial (NCT02418234) from March 2015 to March 2016. Blood samples were drawn within two weeks from PD occurred. T790M mutations were evaluated by droplet digital PCR. We undertook follow-up every 3 months by phone until April 2017. The median follow-up time was 11 months (range, 2 to 22 months).
Result:
Fifty NSCLC patients with BM after EGFR-TKI resistance were collected from our previous trials. After TKI resistance, ten patients received subsequent osimertinib treatment. Finally, ten patients included three males and seven females were included in the study. The median age was 66.5 (56 to 73). Seven were detected acquired T790M mutation. The median survival was 15.3 months (95% CI, 10.1 to 20.6 mo), 15.3 mo for T790M negative and 12.9 mo for T790M positive patients.
Conclusion:
Our preliminary study showed the well efficacy of osimertinib on NSCLC patients with BM. It provides well survival benefit. Randomized control trials should be required before it is widely used.
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-002 - Crizotinib-Associated Toxic Epidermal Necrolysis in an ALK-Positive Advanced NSCLC Patient (ID 7520)
09:30 - 16:00 | Author(s): Xueqin Chen
- Abstract
Background:
Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase (ALK) tyrosine-kinase that has been approved for treating patients with advanced echinoderm microtubule associated protein like 4-anaplasitic lymphoma kinase (EML4-ALK) rearranged non-small-cell lung cancer (NSCLC). Toxic epidermal necrolysis (TEN) is a rare adverse event related to crizotinib.
Method:
We report a case of 75-year-old Chinese male patient of advanced NSCLC harboring with ALK fusion, who developed TEN after 56 days of crizotinib treatment
Result:
the patient demised due to this dermatological adverse event
Conclusion:
The occurrence of severe cutaneous necrolysis that predominantly involve skin and mucous membranes during crizotinib treatment should alert clinicians to be aware of TEN and take prompt actions.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-031 - ctDNA Assessment of EGFR Mutation Status in Chinese Patients with Advanced Non–Small-Cell Lung Cancer in Read World Setting (ID 9173)
09:30 - 16:00 | Author(s): Xueqin Chen
- Abstract
Background:
EGFR mutation in plasma circulating free tumor-derived DNA (ctDNA) by ARMS methods has been widely used in clinical settings in China. However, the prevalence of EGFR mutations in ctDNA was still unknown in the real world. This large-scale study (NCT02623257) aimed to explore the prevalence of EGFR mutations and determine the correlation of EGFR mutation status with clinical characteristics.
Method:
Plasma DNA samples from 721 patients with stage III/IV NSCLC who received ≤1 line chemotherapy were collected from 65 hospitals. EGFR mutations were tested by ARMS method. The EGFR mutation rate was calculated and the associations between EGFR mutant and patients’ demographic data, disease status as well as treatment pattern were explored.
Result:
EGFR mutations were detected in 176 of 721 (24.4%) patients, 165 of 620 (26.6%) in adenocarcinoma and 8 of 85 (9.4%) in squamous carcinoma. 138 (19.1%) harbored sensitizing mutations (66 19del, 62 L858R, 7 G719X, 2 L861Q, and 1 S768I) alone, 20 (2.8%) had resistance mutations (13 T790M, 7 Ins20) alone, 2 (0.3%) had a combination of activating mutations, and 16 (2.2%) had a combination of activating and resistance mutations. Twenty-eight (3.8%) patients were detected de novo T790M mutation either existed alone or combination, but no difference of clinical characteristics was observed. Higher detection rate was observed in 566 chemotherapy-naïve patients than in 155 patients received 1[st] line chemotherapy (27.2% versus 14.2%; p<0.001). Of which, the mutation rate of exon 19 deletion was 11.3% for naïve patients and 8.4% for the patients with 1[st] line chemotherapy; while the mutation rate of L858R decreased most obviously from 11.9%(naïve) to 1.9%(1[st] line). We also noticed 117 patients had ≥ 2 organ metastases and the mutation rate was 35.0% in these patients. Multivariate analysis showed female, chemotherapy native, or patients with ≥2 metastatic organs had higher percentage of EGFR mutation. Additionally, in 194 patients who had the follow-up treatment records, 34 of 49 patients (69.4%) with sensitive EGFR mutations received EGFR-TKI, 96 of 136 (70.6%) patients without sensitive EGFR mutation received chemo±radiation.
Conclusion:
Using plasma samples to detect EGFR mutation is feasible. ctDNA based EGFR mutation test could be a surrogate when tissue biopsy is not available due to limited tissue availability and procedural feasibility.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-040 - Driver Gene Detection in Chinese NSCLC Patients Using cSMART and Prognosis Analysis (ID 9044)
09:30 - 16:00 | Presenting Author(s): Xueqin Chen
- Abstract
Background:
Circulating single-molecule amplification and resequencing technology (cSMART) based on next-generation sequencing is highly sensitive, accurate and quantificational. The purpose of this study is to detect the status of 9 driver genes in Chinese NSCLC patients using cSMART and analyze the associations of gene status, clinical characteristics and prognosis.
Method:
The tissue or plasma samples of 85 patients diagnosed NSCLC from Hangzhou First People’s Hospital were collected. EGFR, KRAS, ALK, ROS1, PIK3CA, c-MET, RET, BRAF and HER2 genes were combined detection using cSMART. The association between gene status and clinical characteristics was analyzed by chi-square test and Fisher’s exact. Kaplan-Meier survival curves were plotted for overall survival (OS) and analyzed with the log-rank test. Cox proportional hazards regression was used for multivariate analysis.
Result:
Amongst 85 NSCLC patients, EGFR mutations were more frequent (57.6%), followed by KRAS mutation (18.8%), ALK mutation (10.6%), ALK fusion (9.4%), MET mutation (9.4%), PI3KCA mutation (8.2%), ROS1 fusion (3.5%), BRAF mutation (1.2%), RET fusion (1.2%) and HER2 mutation was not found. Furthermore, the abundances of gene mutation were relatively low. The EGFR mutation rate was higher in patients with adenocarcinoma histology than in those with squamouscarcinoma histology (P=0.03). T790M mutation was more common in patients with a history of TKI treatment (P<0.01) and acquired T790M mutation was often accompanied by the original sensitive mutation (P<0.01). ALK fusion was more easily detected in tissue sample. All 8 MET gene exon14 skippings were found in adenocarcinoma histology and this gene alteration often happened after TKI treatment (P=0.02). OS was significantly improved in the EGFR mutation group compared with the wild group (median 32m vs 19m) (P=0.05). No significant survival difference between KRAS mutation and wild group was found (P>0.05). Among EGFR wild advanced NSCLC patients, the median OS of KRAS mutation group was 13 months while that of wild group was 26 months, but there was no significant difference (P>0.05). Multivariant analyses showed gender, TKI treatment history and smoking history were independent prognostic factors in NSCLC(P<0.05)．
Conclusion:
EGFR mutation is the most common driver gene in Chinese NSCLC, especially in adenocarcinoma patients, which often occurs in exon 19、20 and 21 region. Then followed by KRAS mutation, it mostly occurs in exon 2. MET gene exon14 skipping is common in patients with adenocarcinoma or post-TKI treatment, which may be related to TKI resistance. Gender, smoking history and TKI treatment history could be independent prognostic factors in NSCLC.
