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Y. Jin
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JCES01 - Joint IASLC - Chinese Society for Clinical Oncology - Chinese Alliance Against Lung Cancer Session (ID 413)
- Event: WCLC 2016
- Type: Joint Chinese / English Session
- Track:
- Presentations: 2
- Moderators:F.R. Hirsch, C. Bai
- Coordinates: 12/04/2016, 08:00 - 11:45, Stolz 1
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JCES01.09 - A Comparison of ddPCR and ARMS for Detecting EGFR T790M Status from Advanced NSCLC Patients with Acquired EGFR-TKI Resistance (ID 7053)
10:10 - 10:20 | Author(s): Y. Jin
- Abstract
- Presentation
Background:
To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy.
Methods:
To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy.To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy.
Results:
A total of 108 patients were enrolled in this study. 108 patient plasma samples were detected by ddPCR and 75 were detected by ARMS. And 16 patients experienced re-biopsy were detected T790M status by ARMS method. 43.7% (47/108) had acquired T790M mutation by ddPCR. In 75 patient plasma samples, comparing ddPCR with ARMS, the rates of T790M mutation were 46.7% (35/75) and 25.3% (19/75) by ddPCR and ARMS, respectively. Of all, 16 patients both had tumor and plasma samples, the T790M mutation rates were 56.3% (9/16) by ARMS in tissue and 50.5% (8/16) by ddPCR in plasma ctDNA. Among them, there were two ctDNA T790M mutations by ddPCR but T790M gene negative in tumor tissue by ARMS method. For all patients, the median PFS and OS were 12.3 months and 32.8 months, respectively. The patients with T790M-positive tumors had a longer time to disease progression after treatment with EGFR-TKIs (median, 13.1 months vs 10.8 months; P=0.010) and overall survival (median, 35.3 months vs 30.3 months; P=0.214) compared with those with T790M-negative patients.
Conclusion:
Our study demonstrates dPCR assay provide feasibility and sensitive method in detecting EGFR T790M status in plasma samples from NSCLC patients with acquired EGFR-TKI resistance.And T790M-positive patients have better clinical outcomes to EGFR-TKIs than patients with T790M negative.
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JCES01.14 - Mutational Profiling of Non-Small-Cell Lung Cancer Patients Resistant to First-Generation EGFR Tyrosine Kinase Inhibitors Using next Generation Sequencing (ID 7056)
11:10 - 11:10 | Author(s): Y. Jin
- Abstract
Background:
Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epithelial growth factor receptor (EGFR) mutations invariably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Although previous research have identified several mechanisms of resistance, the systematic evaluation using next generation sequencing (NGS) to establish the genomic mutation profiles at the time of acquired resistance has not been conducted.
Methods:
In our single center, we performed NGS of a pre-defined set of 416 cancer-related genes in a cohort of 97 patients with NSCLC harboring TKI-sensitive EGFR mutations at the time of acquired resistance to first-generation EGFR-TKIs between January 2015 to December 2015.
Results:
In 97 samples we found total 345 gene alterations (mean 3.6 mutations per patient, range 1-10). Fifty-six patients (57.7%) still exhibit EGFR-sensitive mutations as pretreatment, 93 patients (95.9%) exhibit at least one mutation except for previous existed EGFR-sensitive mutations. In all the 97 patients, most frequently mutated genes were TP53 (59.8%), T790M (28.9%), TET2 (11.3%), EGFR amplification (10.3%), PIK3CA (8.2%), BIM (8.2%), KRAS (7.2%), APC (7.2%), RB1 (7.2%), HER2 (6.2%), DNMT3A (6.2%) and MET (5.2%).
Conclusion:
NGS in this study uncovered many new genetic alterations potentially associated with EGFR TKI resistance and provided information for the further study of drug resistance and corresponding relevant tactics against the challenge of disease progression.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 4
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-040 - A Comparison of ddPCR and ARMS for Detecting EGFR T790M Status from Advanced NSCLC Patients with Acquired EGFR-TKI Resistance (ID 3727)
14:30 - 14:30 | Author(s): Y. Jin
- Abstract
Background:
To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy.To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy.
Methods:
A comparison of two platforms for detecting EGFR mutations in plasma ctDNA was undertaken. Plasma samples and tumor samples were collected from patients happening acquired EGFR-TKI resistance in Zhejiang cancer hospital from December 2014 to December 2015. Extracted ctDNA was analyzed using two platforms (Droplet Digital PCR and ARMS [dPCR]). And the associations between progression free survival (PFS) starting from initial TKI treatment and the T790M ctDNA status detected in plasma were analyzed.
Results:
A total of 108 patients were enrolled in this study. 108 patient plasma samples were detected by ddPCR and 75 were detected by ARMS. And 16 patients experienced re-biopsy were detected T790M status by ARMS method. 43.7% (47/108) had acquired T790M mutation by ddPCR. In 75 patient plasma samples, comparing ddPCR with ARMS, the rates of T790M mutation were 46.7% (35/75) and 25.3% (19/75) by ddPCR and ARMS, respectively. Of all, 16 patients both had tumor and plasma samples, the T790M mutation rates were 56.3% (9/16) by ARMS in tissue and 50.5% (8/16) by ddPCR in plasma ctDNA. Among them, there were two ctDNA T790M mutations by ddPCR but T790M gene negative in tumor tissue by ARMS method. For all patients, the median PFS and OS were 12.3 months and 32.8 months, respectively. The patients with T790M-positive tumors had a longer time to disease progression after treatment with EGFR-TKIs (median, 13.1 months vs 10.8 months; P=0.010) and overall survival (median, 35.3 months vs 30.3 months; P=0.214) compared with those with T790M-negative patients.
Conclusion:
Our study demonstrates dPCR assay provide feasibility and sensitive method in detecting EGFR T790M status in plasma samples from NSCLC patients with acquired EGFR-TKI resistance.And T790M-positive patients have better clinical outcomes to EGFR-TKIs than patients with T790M negative.
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P3.02b-074 - Brain Radiotherapy with EGFR-TKI Plays an Important Role in 181 EGFR Mutant Non-Small Cell Lung Cancer Patients with Brain Metastasis (ID 6371)
14:30 - 14:30 | Author(s): Y. Jin
- Abstract
Background:
To perform a retrospective analysis of patients with epidermal growth factor receptor (EGFR)-mutant NSCLC patients who developed brain metastases (BM) to assess the appropriate use of EGFR tyrosine kinase inhibitors (TKIs), and radiation therapy (RT) for symptomatic and asymptomatic BM.
Methods:
There were 482 patients diagnosed with EGFR mutant NSCLC between June 2006 and December 2015 at Zhejiang Cancer Hospital. Treatment outcomes had been retrospectively evaluated in 181 patients with 132 asymptomatic BM and 49 symptomatic BM. 39 patients received first-line brain RT, 23 patients received delayed brain RT, and 34 patients did not receive brain RT. In all 49 symptomatic BM patients received radiotherapy, except 4 patients were refusal of treatment. There were 45 patients had brain radiotherapy, 39 received WBRT and 6 were SRS. Among 132 asymptomatic brain metastasis patients, 74 received radiotherapy (63 WBRT and 11 SRS). The BM of 26 patients had still stable by the follow-up time. 22 patients did not get information about brain RT after intracranial progression and until the last follow-up. 10 patients were refusal of brain RT treatment.
Results:
In 49 symptomatic BM patients, 45 received RT including 40 WBRT and 5 SRS. Among 6 SRS. The iPFS for patients treated with SRS and WBRT was 12.4 months and 9.5 months (P=0.895). Median OS in the SRS group was also greater than in those treated with WBRT (37.7 vs 21.1 months)(P=0.194). In the group of 132 asymptomatic BM patients, There were 86 patients who had not received brain radiotherapy before TKI and 46 received RT whether upfront or concurrent TKI. The median OS in the upfront RT group was also longer than in the upfront TKI (24.9 vs 17.4 months)(P=0.035). Further analysis with subgroup to the timing of using radiotherapy, among the 74 patients, 33 underwent concurrent TKI and radiation therapy, 13 were given TKI after failure of first-line radiotherapy plus chemotherapy and 28 patients received radiotherapy after TKI. The iPFS of three groups was 11.1 months, 11.3 months and 8.1 months (P=0.032). The mOS of three groups was 21.9 months, 26.2 months and 17.1 months(P=0.085).
Conclusion:
The study suggests that the deferral of brain RT may result in inferior OS in NSCLC patients harboring EGFR mutations and asymptomatic BM. For now, the standard-of-care treatment for newly diagnosed BM whether symptomatic or asymptomatic brain metastases should remain upfront RT followed by EGFR-TKI therapy. First-line brain RT may improve long-term survival in EGFR mutation patients.
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P3.02b-093 - Zoledronic Acid Enhances the Effects of Icotinib on Non-Small Cell Lung Cancer Patients with Bone Metastases (ID 3958)
14:30 - 14:30 | Author(s): Y. Jin
- Abstract
Background:
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are widely used as molecularly targeted drugs for the treatment of non-small cell lung cancer (NSCLC), with icotinib being one such EGFR-TKI. Bone metastases occur in 30–40 % of patients with advanced non-small cell lung cancer (NSCLC). Zoledronic acid is a third-generation bisphosphonate, and is effective for the reduction of the skeletal-related events (SREs). In addition, some reports have described the possibility of direct and indirect antitumor effects of zoledronic acid. However, most of these studies are preclinical research or combination with chemotherapy.
Methods:
We retrospectively analyzed data of 184 patients received icotinib with progression-free survival more than 6 months and used zoledronic acid at least once from July 2011 to May 2015 in Zhejiang cancer hospital. Progression free survival (PFS) and overall survival (OS) were calculated with the Kaplan-Meier method. Multivariate regression was performed using the Cox proportional hazards model.
Results:
A total of 184 NSCLC patients with bone metastases were treated with zoledronic acid and icotinib. 140 (76.1%) patients were with EGFR mutations (75 with deletions within exon 19, 63 with L858R messenger mutation in exon 21 and 2 with G719X mutation in exon 18). Median PFS of all patients during icotinib treatment was 10.7 months. The median overall survival (OS) time for all patients was 24.3 months. The PFS in ≥1 year and <1 year zoledronic group were 12.1 months and 10.2 months (P=0.351). And the PFS in the group of ≥2 years ZOL was longer than the group of <2 years zoledronic treatment (12.2 versus 10.5 months, P=0.175). The cumulative incidences of bone pain had not increased during 1 year zoledronic treatment than before ZOL treatment (31.0% versus 45.1%). 39 of the 92 patients in ≥1 year zoledronic treatment (39.1%) and 24 of the 92 patients in <1 year zoledronic (26.1%) experienced SREs before zoledronic acid treatment (P = 0.059). During zoledronic acid treatment, the incidence rate of SREs in group of ≥1 year and <1 year were 17.4% (16/92) and 13.0% (12/92), respectively.
Conclusion:
Hence, combined treatment of EGFR-TKI with zoledronic acid may have a more effective for NSCLC with bone metastases, particularly in EGFR mutation patients.
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P3.02b-105 - Mutational profiling of non-small-cell lung cancer patients resistant to first-generation EGFR tyrosine kinase inhibitors using next generation sequencing (ID 3801)
14:30 - 14:30 | Author(s): Y. Jin
- Abstract
Background:
Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epithelial growth factor receptor (EGFR) mutations invariably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Although previous research have identified several mechanisms of resistance, the systematic evaluation using next generation sequencing (NGS) to establish the genomic mutation profiles at the time of acquired resistance has not been conducted.
Methods:
In our single center, we performed NGS of a pre-defined set of 416 cancer-related genes in a cohort of 97 patients with NSCLC harboring TKI-sensitive EGFR mutations at the time of acquired resistance to first-generation EGFR-TKIs between January 2015 to December 2015.
Results:
In 97 samples we found total 345 gene alterations (mean 3.6 mutations per patient, range 1-10). Fifty-six patients (57.7%) still exhibit EGFR-sensitive mutations as pretreatment, 93 patients (95.9%) exhibit at least one mutation except for previous existed EGFR-sensitive mutations. In all the 97 patients, most frequently mutated genes were TP53 (59.8%), T790M (28.9%), TET2 (11.3%), EGFR amplification (10.3%), PIK3CA (8.2%), BIM (8.2%), KRAS (7.2%), APC (7.2%), RB1 (7.2%), HER2 (6.2%), DNMT3A (6.2%) and MET (5.2%).
Conclusion:
NGS in this study uncovered many new genetic alterations potentially associated with EGFR TKI resistance and provided information for the further study of drug resistance and corresponding relevant tactics against the challenge of disease progression.
