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Rongrong Chen
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MA16 - Novel Mechanisms for Molecular Profiling (ID 917)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 203 BD
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MA16.06 - EGFR Clonality and Tumor Mutation Burden (TMB) by Circulating Tumor DNA (ctDNA) Sequencing in Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 13146)
14:05 - 14:10 | Author(s): Rongrong Chen
- Abstract
- Presentation
Background
TKI has significantly improved survival time of NSCLC pts with sensitive mutation. However, pts present different outcome while receiving TKI treatment. We conduct a prospective multicenter clinical trial to determine whether clonality of sensitive mutation is related to the efficacy of TKI. We also evaluate the consistency of TMB between tissue and blood in this cohort.
a9ded1e5ce5d75814730bb4caaf49419 Method
Paired tumor and plasma samples at diagnosis were obtained from systemic treatment naïve pts with advanced NSCLC. DNA was sequenced by target-capture deep sequencing of 1021 previously annotated genes related to solid tumors. Clonal EGFR mutation was defined if EGFR mutation was in the cluster with the highest mean variated allele frequency with PyClone, and otherwise subclonal EGFR mutation. TMB of tissue (tTMB) and blood (bTMB) analysis interrogated single nucleotide variants, small insertion and deletion, with VAF ≥3 % and ≥0.5 %, respectively. TMB-high pts were identified with ≥9 mut/MB (upper quartile of data from geneplus).
4c3880bb027f159e801041b1021e88e8 Result
During February 2017 to April 2018, 127 advanced NSCLC pts were enrolled from 9 centers. A total of 653 somatic variations were detected in tissues. Mutations occurred most frequently in EGFR (57 %), TP53 (54 %), KRAS (9 %), ALK (8 %). In matched plasma, 405 (62 %) tumor-derived mutations were detected by pan-caner panel sequencing. A total of 90 EGFR mutations were detected in 73 pts, most of which occurred in tyrosine kinase domain (L858R, 41%; Ex19del, 33%). Most EGFR mutation were clonal in tissue and plasma, with a consistence of 83 % in paired samples. In addition, bTMB was significantly correlated to tTMB (Pearson r= 0.85, p-value= 1.8e-30), with a consistence of 89 %. Interestingly, high TMB was observed in a small fraction of patients (8 %) with driver mutations, such as mutations in EGFR, ALK fusion, ERBB2 and PIK3CA.
8eea62084ca7e541d918e823422bd82e Conclusion
Deep sequencing with the pan-cancer panel can effectively detect mutations and evaluate TMB in both tissue and blood with high consistence. EGFR mutations can be clonal or subclonal in both tissue and blood. Prospective multicenter study is ongoing to determine the EGFR clonality as a predictive factor for the TKI efficacy in NSCLC (TRACELib-NSCLC, NCT03059641).
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 3
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-105 - Lung Cancer Patients with Concurrent EGFR and MET Mutations: A Retrospective Analysis of 29 Cases (ID 12864)
16:45 - 18:00 | Author(s): Rongrong Chen
- Abstract
Background
It has been reported that about 5%-20% of EGFR-TKIs resistant NSCLC patients harbors MET amplification or activating mutations. However, the extent that MET abnormal activation contributes to EGFR-TKIs resistance remains widely unknown. Here, we describe the clinical and genetic characteristics of 29 lung cancer patients harboring concurrent EGFR and MET mutations.
a9ded1e5ce5d75814730bb4caaf49419 Method
Genetic mutations were reviewed in 6000 lung cancer patients who underwent genetic testing at our institute from 2016 to 2018. Mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes).
4c3880bb027f159e801041b1021e88e8 Result
The selected patients included 24 lung adenocarcinoma patients, 1 squamous cell lung cancer patient and 3 lung cancer patients with unspecified pathology. Both MET amplification and activating mutations were included for analysis. MET amplification was detected in 90% (27/30) of samples, while activating mutations was present in 13.3% (4/30) of samples, including H1112Y, D1228N, D1246Y and D1246H. 14% (4/29) of patients had not received EGFR-TKIs treatment before genetic testing, which were considered as primary resistance. 79% (23/29) of patients were treated with EGFR-TKIs. Surprisingly, 60% (18/30) of cases had other functional mutations which may also affect the effectiveness of EGFR-TKIs, such as EGFR T790M mutation (3 cases), rare EGFR mutations (I744M, R108K and C769S, 3 cases), EGFR amplification (7 cases), CDK4 amplification (2 cases), loss-of-function mutations of CDKN2A (2 cases) and so on. One patient had two samples tested. He was resistant to gefitinib and osimertinib, and EGFR L858R mutation and MET amplification were detected in the first sample. Later, he was treated with combined gefitinib and crizotinib and reached PR at the 2nd month. However, his disease finally progressed probably due to an additional MET mutation (D1246Y) that caused resistance to crizotinib.
8eea62084ca7e541d918e823422bd82e Conclusion
MET amplification and activating mutations may lead to primary and acquired resistance of EGFR-TKIs. Moreover, additional potentially resistant mechanisms were detected in most cases. Therefore, it is apparently requisite to provide a comprehensive genetic testing to lung cancer patients.
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P1.01-27 - Influence of EGFR-TKIs Treatment Lines and PFS on the Emergence of T790M Mutation (ID 13584)
16:45 - 18:00 | Author(s): Rongrong Chen
- Abstract
Background
For sensitizing EGFR mutation positive lung cancer patients, EGFR-TKIs can be used as the first-line or second-line (after chemotherapy) therapy according to NCCN guideline. However, whether different lines of EGFR-TKIs therapy or different PFS would affect the emergence of T790M, the leading cause of resistance to first and second generation of EGFR-TKIs was unknown.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively analyzed 142 advance NSCLC patients with 93 patients received 1st-line EGFR-TKIs, and 49 patients received 2nd-line EGFR-TKIs after chemotherapy. EGFR sensitizing mutation and T790M mutation was detected simultaneously by hybridization capture-based NGS panel sequencing with tumor biopsy , ctDNA or pleural effusion samples.
4c3880bb027f159e801041b1021e88e8 Result
For the patients received 1st-line EGFR-TKIs, 47 carried L858R mutation and 46 carried EX19del mutation; while patients received 2nd-line EGFR-TKIs, 24 carried L858R mutation and 25 carried EX19del mutation. When those patients progressed on TKIs, T790M emerged in 25 of the 47 (53.19%) L858R carriers, and 23 of the 46 (50.00%) EX19del carriers with 1st-line EGFR-TKIs (p=0.76). However, only 6 of the 24 (25.00%) L858R carriers yet 16 of the 25 (64.00%) EX19del carriers with 2nd-line EGFR-TKIs had T790M detected (p=0.006). The incidence of T790M was significant lower in L858R carrier treated with 2nd-line compared with 1st-line EGFR-TKIs (25.00% vs 53.19%, p=0.023), however, there was no difference for EX19del carrier (50.00% vs 64.00%, p=0.26). To further analyzed whether different PFS affected the appearance of T790M, we divided patients into 3 groups as PFS≥13 months (n=48), PFS≤8 months (n=60) and the between (n=34). The incidence of T790M was significantly lower in the PFS≤8 months group compared with the PFS≥13 months (31.67% vs 62.5%, p=0.001). The difference was also significant if only counting the L858R carriers (18.52% vs 59.26%, p=0.002), but not significant in the EX19del carriers (42.42% vs 66.67%, p=0.082).
8eea62084ca7e541d918e823422bd82e Conclusion
1st-line or 2nd-line EGFR-TKIs generally did not significantly alter the emergence of T790M. But for the L858R mutation carriers, the incidence of T790M is significantly decreased if treated as a 2nd-line EGFR-TKIs therapy. In addition, patients with longer PFS were associated with higher incidence of T790M mutation.
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P1.01-56 - Concurrent Mutations in Chinese Lung Cancer Patients Carrying HER2 Genomic Aberrations (ID 13756)
16:45 - 18:00 | Author(s): Rongrong Chen
- Abstract
Background
Although human epidermal growth factor receptor 2 (HER2, ERBB2) genomic aberration has been identified as therapeutic targets, clinical trials of HER2-directed therapies have disappointing results in lung cancer. We hypothesize that the concurrent alterations might be one of the reasons, thus the aim of this study was to describe frequent concurrent alterations in Chinese lung cancer patients harboring HER2 mutations.
a9ded1e5ce5d75814730bb4caaf49419 Method
A total of 147 cancer patients with HER2 mutations were enrolled in the study. Tumor biopsy, ctDNA and pleural effusion samples were collected for detection alterations using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (59-1021).
4c3880bb027f159e801041b1021e88e8 Result
Sixty-two of 147 patients with HER2 genomic aberrations were diagnosed as lung cancer. The HER2 gene was amplified in 11 (18%) patients, whereas HER2 mutations were detected in 48 patients, co-occurrence of HER2 amplification and mutations were in 3 patients. Thirty of the 62 patients (48.39%) had concurrent actionable mutations across 18 genes, which involved in RTK-PIK3CA-mTOR signaling pathways, cell-cycle pathway, DNA repair pathway, RAS-RAF-MAPK pathway and some others (details in table). Moreover, 7 patients had more than 2 concurrent mutations besides HER2 mutation/amplification.
Table 1. concurrent genetic alterations in HER2-altered lung cancer patients
Signaling pathway Concurrent
actionable
mutations
Number of
patients
RTK-PIK3CA-mTOR
EGFR 11 PIK3CA 4 STK11 2 FBXW7 1 TSC1 1 FLCN 1 C11orf30 1 Cell-cycle CDKN2A 5 CCND1 2 RB1 1 DNA repair BRCA2 1 ATM 1 RAS-RAF-MAPK BRAF 1 KRAS 1 Others MDM2 2 JAK2 2 SMARCA4 2 PTCH1 1
8eea62084ca7e541d918e823422bd82e Conclusion
Concurrent of actionable genetic alterations in HER2-altered Chinese lung cancer patients was common. The complex molecular profiles elucidate the importance of comprehensive analysis of genetic mutations when considering anti-HER2 targeted therapy.
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.13-08 - Distribution, Differences in Clinical Characteristics and Resistance Mechanism of ALK Variants in Chinese Lung Cancer Patients. (ID 13678)
16:45 - 18:00 | Author(s): Rongrong Chen
- Abstract
Background
ALK rearrangements are established targetable drivers in NSCLC. Recent reports indicate differential progression-free survival to ALK inhibitors according to specific EML4-ALK variant.
a9ded1e5ce5d75814730bb4caaf49419 Method
A total of 172 unique Chinese lung cancer patients with tumors harboring ALK rearrangements (ALK+) were enrolled in the study from 2016 to 2018. ALK+ were detected by Ventana, FISH, or next-generation sequencing based ER-Seq method, which enables simultaneously assess single-nucleotide variants, insertions/deletions, rearrangements, and somatic copy-number alterations across at least 59 genes (59-1021). Tissue biopsy was the first choice for NGS mutation profiling, and ctDNA or pleural effusion testing was used as an alternative.
4c3880bb027f159e801041b1021e88e8 Result
Of these 172 cases, the median diagnosis age was 50 (range 24-78), 58% were female, 90% was NSCLC. Of the 147 ALK+ cases detected by NGS, we identified 65 (44%) EML4-ALK v1 (E13; A20), 18 (12%) EML4-ALK v2 (E20; A20), 43 (29%) EML4-ALK v3 (E6; A20), 13 (9%) other EML4-ALK, and 8 (5%) non-EML4-ALK rearrangements. 2 new fusion genes were found in non EML4-ALK rearrangements (SRBD1-ALK (EX20; EX20) and CLIP4-ALK (EX9; EX20)), and the CLIP4-ALK patient’s tissue was also ALK positive by Ventana. V1 found a higher proportion of pleural effusion at baseline than non-v1 (12% v.s.5%). Mutation profiling by NGS were performed after disease progression in 55 patients treated with crizotinib. mPFS was 8.1 months, no significant difference existed between v1 and v3 (P=0.69). But the presence of known ALK resistance mechanisms was significantly higher in v3 as compared to non-v3 (67% v.s. 27%, P=0.038).
8eea62084ca7e541d918e823422bd82e Conclusion
Next generation sequencing allows for detection of the specific ALK fusion partner and variants, increases the understanding of the biology of ALK+ NSCLC, and may have value to foretell potential mechanisms of resistance.
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 3
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-100 - Different Genetic Mutations Enriched in Circulating Tumor DNA Predict Different Metastatic Sites in Lung Adenocarcinoma Patients (ID 13636)
16:45 - 18:00 | Author(s): Rongrong Chen
- Abstract
Background
The mutation map of the lung adenocarcinoma is clear. However, differences of genetic mutations related to metastatic sites have not been addressed before and remain to be explored. Identification of mutation signature may help to predict metastasis.
a9ded1e5ce5d75814730bb4caaf49419 Method
We reviewed 353 ctDNA samples from lung adenocarcinoma patients with definite metastasis at our institute. Somatic mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of 59 genes.
4c3880bb027f159e801041b1021e88e8 Result
All the samples were divided into 2 groups based on the distance of the metastases: 165 samples was in the distal metastasis group including bone or liver metastases; 188 samples was in the proximal group, including lung, pleural or thoracic lymph node metastasis. The gene mutation number of the distal metastasis is higher than the proximal metastasis (4.92 vs 3.85, P=0.031). Gene mutations for each group are shown in the figure below. Similar to the genetic profiling of lung adenocarcinoma in COMIC database, the most frequently mutated genes were EGFR and TP53 in two groups. But the frequency mutation of NTRK1 in proximal metastasis group is three times more than that of the distal metastasis group (11/188, 5.9% vs 3/165,1.8%). And the frequency of ALK mutation in the distal metastasis group is two times more than that of the proximal metastasis group (10/165, 6.1% vs 6/188, 3.2%). Moreover, for the top 9 frequently mutant genes, there was 78% overlap in the two groups. However, the overlap with COSMIC database was 55% for distal metastasis group and 44% for the proximal metastasis.
8eea62084ca7e541d918e823422bd82e ConclusionDistant metastasis group
Proximal metastasis group
COSMIC database
gene
Mutation frequency
gene
Mutation frequency
gene
Mutation frequency
1
EGFR
70.30%
EGFR
73.94%
EGFR
31%
2
TP53
60.61%
TP53
61.17%
TP53
31%
3
KRAS
11.52%
ERBB2
9.04%
KRAS
18%
4
RB1
10.30%
KRAS
9.04%
STK11
8%
5
NF1
9.70%
RB1
7.45%
CDKN2A
7%
6
ERBB2
7.88%
NF1
7.40%
SMARCA4
6%
7
APC
6.67%
APC
6.91%
NF1
6%
8
ALK
6.06%
PIK3CA
6.38%
ATM
5%
9
ATM
6.06%
RET
5.85%
KDR
5%
10
PIK3CA
6.06%
NTRK1
5.85%
Lung adenocarcinoma patients with ALK mutation are more likely to have distant metastasis. While the patients with NTRK1 mutation are more likely to have proximal metastasis.
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P2.01-107 - Analysis of Mutation Detection by ctDNA on the Basis of Metastatic Sites in Lung Adenocarcinoma Patients (ID 13635)
16:45 - 18:00 | Author(s): Rongrong Chen
- Abstract
Background
Circulating tumor DNA (ctDNA) testing represents a powerful tool to detect gene alterations in patients. However, differences in mutation detected by ctDNA related to metastatic sites in lung cancer have not been addressed before and remain to be explored.
a9ded1e5ce5d75814730bb4caaf49419 Method
We reviewed 317 ctDNA samples from 310 lung adenocarcinoma patients with definite metastasis at our institute. Somatic mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of 1021 genes.
4c3880bb027f159e801041b1021e88e8 Result
Patients were divided into two groups according to metastatic sites. Any case with metastasis to the bone, liver or adrenal gland falls into the major organ metastasis group, while any case with metastasis to the lung, pleura or lymph node belongs to the local metastasis group. No genetic alteration was detected in 14 (11.5%) of 122 samples in the major organ group and 35 (17.9%) of 195 in the local group. And distant metastasis is associated with more mutations on average detected by ctDNA (5.26 for the major organ group vs 3.72 for the local group; p=0.0039). As for genes involved, the most common mutated ones are EGFR and TP53 for both groups, with an overall mutation rate being 40.6% and 33.2% respectively. And just as average gene alterations mentioned above, the mutation rates of EGFR and TP53 are much higher in the major organ group (49.6% vs 35.2% for EGFR; 43.6% vs 26.9% for TP53). Besides, mutations of NF1, MLL3, KRAS and KEAP1 are more frequent in the major organ group while mutation rate of PIK3CA is slightly higher in the local group (Table).
8eea62084ca7e541d918e823422bd82e ConclusionTable. Some mutated genes detected by ctDNA
major organ metastasis (117)
local metastasis (193)
EGFR
58 (49.6%)
68 (35.2%)
TP53
51 (43.6%)
52 (26.9%)
KRAS
9 (7.7%)
7 (3.6%)
MLL3
9 (7.7%)
6 (3.1%)
NF1
9 (7.7%)
3 (1.6%)
ERBB2
5 (4.3%)
6 (3.1%)
PIK3CA
3 (2.6%)
7 (3.6%)
KEAP1
7 (6.0%)
3 (1.6%)
More gene alterations were detected by sequencing of ctDNA in patients of lung adenocarcinoma with major organ metastasis compared to those with only local metastasis.
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P2.01-117 - Concurrent Gene Alterations in Treatment-Naïve EGFR-Mutant Advanced Non-Small Cell Lung Cancer (ID 13102)
16:45 - 18:00 | Author(s): Rongrong Chen
- Abstract
Background
EGFR-TKIs is the standard first line treatment for EGFR-mutant advanced non-small-cell lung cancer (NSCLC). However, 20% to 30% of patients who receive EGFR-TKIs exhibit primary resistance. The gene alterations in treatment-naïve EGFR-mutant advanced NSCLC should be better explored.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed gene test results of 980 treatment-naïve advanced NSCLC samples in our institute. Tumor biopsy, ctDNA, pleural effusion or cerebrospinal fluid samples were analyzed using hybridization capture-based NGS ER-seq method, white blood cells as control, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number(CNV) variation at least 59 genes (range 59-1021 genes).
4c3880bb027f159e801041b1021e88e8 Result
Three hundreds and eighty one cases with EGFR sensitive mutation were identified, 358 adenocarcinoma, 7 squamous cell carcinoma, 1 adenosquamous carcinoma and 15 NSCLC. Among the patients, 88 patients (23.1%) harbored concurrent actionable mutations with EGFR, which 43 were exon 19 deletion, 37 were L858R and 8 were uncommon EGFR mutations. One patient had co-occurring L858R, T790M and CDKN2A frameshift mutation. The actionable mutations were from 23 genes, which involved in cellular signaling pathways, and some genes had been reported associated with EGFR-TKIs resistance (details in table). Except the actionable mutations, TP53 mutations were detected in 225 samples (59.1%, 225/381), which 35.1% (79/225) in exon8. Bcl-2–like 11(BIM) deletion were detected in 31 (8.1%, 31/381) white blood cells.
Signaling Pathways
Concurrent gene alterations
Frequency(N=88)
Cell cycle*
CDKN2A
3.9%
CDK4
2.1%
CCNE1
0.8%
CCND1
0.8%
CCND3
0.3%
PI3K/AKT/mTOR*
PIK3CA
2.9%
PTEN
1.3%
TSC1/2
1.0%
AKT2
0.3%
NF1
0.3%
RTKs*
MET
0.8%
HER2
0.8%
FGFR2
0.3%
FGFR3-TACC3
0.3%
Ras/Raf/MAPK*
KRAS
0.8%
Homologous Recombination Repair pathway
BRCA2(sc+gm)
0.8%
BRCA1(sc)
0.5%
ATM
0.5%
PALB2
0.3%
Others
CTNNB1
2.9%
MDM2
2.4%
SMARCA4
0.8%
JAK2
0.5%
sc, somatic mutation;
gm, germline mutation;
*, genes had been reported associated with EGFR-TKIs resistance
8eea62084ca7e541d918e823422bd82e Conclusion
Concurrent gene alterations in treatment-naïve EGFR-mutant advanced NSCLC is common, and mutiple genes are involved. This maybe contribute to the primary resistance to EGFR-TKIs in EGFR-mutant advanced NSCLC. Indicate the importance of multiplex molecular test and further researches of target therapies.
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P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.06-39 - Next Generation Sequencing Reveals Genetic Landscape of Malignant Mesothelioma (ID 12702)
16:45 - 18:00 | Author(s): Rongrong Chen
- Abstract
Background
Malignant mesothelioma (MM) is a rare form of cancer affecting the mesothelium lining. The 5-year survival rate of advanced patients is less than 1% due to the lack of effective medical therapies. To investigate the possibility of targeted therapy for MM patients, a deeper understanding of the genetic basis is required.
a9ded1e5ce5d75814730bb4caaf49419 Method
We reviewed 26 samples taken from 22 MM patients who underwent genetic testing at our institute from 2016 to the present. Somatic mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes).
4c3880bb027f159e801041b1021e88e8 Result
The 26 samples included 8 tumor tissue samples, 17 blood samples and 1 ascetic fluid sample. The most frequently mutated genes were TP53 (11/21), followed by NF2 (6), RB1 (4), NF1 (3), FLT1 (3), BAP1 (2), EGFR (2), FAT2 (2), FGFR4 (2), KIT (2), MAP3K1 (2), MLL4 (2), STK11 (2), APC, ATR, BRAF, BRCA2, CDKN2A, ERBB3, FBXW7, MET, KRAS, PIK3CA and so on. Among these mutations, 5 of NF2 mutations and 2 of NF1 mutations were loss-of-function mutations, which suggests the possible sensitivity of mTOR inhibitors administration. Besides, patients with the active or inactive mutations of KRAS, BRAF, CDKN2A, ERBB3, MET and PIK3CA gene might be sensitive to corresponding targeted drugs. MET exon 14 skipping mutation, commonly identified in non-small-cell cancer (NSCLC) patients, had never been reported in MM patients before. c-Met inhibitors such as crizotinib and cabozantinib may be of efficacy for this patient. Apart from predicting therapeutic effectiveness of MEK inhibitors, the detection of KRAS activating mutation may also provide prognostic information.
8eea62084ca7e541d918e823422bd82e Conclusion
NGS can identify genetic mutations comprehensively and provide predictive and prognostic implications for MM patients. It is a cost-effective tool to describe the genetic landscape of MM, which will facilitate the development of novel therapeutics for the treatment of MM patients.
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P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.01-106 - Real-World Data to Evaluate the Clinical Benefit of NGS for Directing Lung Adenocarcinoma Treatment (ID 12870)
12:00 - 13:30 | Author(s): Rongrong Chen
- Abstract
Background
Since mid-2017, multiple NGS-based companion diagnostic tests have been approved in NSCLC to select patients eligible for targeted therapy and immunotherapy. Here, we retrospectively analyzed the benefit of NGS for advanced lung adenocarcinoma in routine clinical practice.
a9ded1e5ce5d75814730bb4caaf49419 Method
From 2016 to 2018, the samples taken from 9 lung adenocarcinoma patients were sent to Geneplus-Beijing Institute for genetic testing. Mutation profiles were analyzed using hybridization capture based NGS, which enables the simultaneous detection of single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations of at least 59 genes (range 59 – 1021 genes). The tumor response was evaluated using RECIST v1.1.
4c3880bb027f159e801041b1021e88e8 Result
Six tumor tissue samples, two blood samples and one pleural effusion sample were analyzed (Table 1). No actionable mutation was detected in patient 1 and then he left hospital without additional treatment. The KRAS mutation present in patient 2 suggested that he might be resistant to EGFR-TKIs. Therefore, he received chemotherapy. According to the genetic testing results, all the other patients received EGFR-TKIs and the disease control rate was 100% at the 2nd month. Apart from EGFR T790M mutation, EGFR amplification was present in patient 8 with disease progression following gefitinib therapy. She received osimertinib and achieved PR at the 2nd month. The response has maintained for over 7 months up to now, which made us reconsidering the controversial correlation between EGFR amplification and EGFR-TKI effectiveness. Rare EGFR mutation and MET amplification were detected in patient 9, and then he was treated with icotinib.The best response was SD at the 4th month. However, he died of pulmonary embolism or cerebral infarction, making the duration of response 4 months.
8eea62084ca7e541d918e823422bd82e ConclusionTable 1. Clinical and genetic characteristics of 9 patients Patient No Age/Gender Sample Previous Targeted Therapy Actionable Mutations Following Treatment Response Evaluation (2nd month) Duration of response (months) 1 72/Male Blood No No No treatment Not applicable Not applicable 2 62/Male Tissue No KRAS p.G12A, STK11 p.D53Gfs*110 Chemotherapy Not available Not available 3 62/Male Tissue No EGFR p.L747_T751del (EX19del) Gefitinib PR 20+ 4 63/Female Tissue No EGFR p.L858R (EX21) Gefitinib PR 5+ 5 75/Female Tissue No EGFR p.L858R (EX21) Icotinib SD 11+ 6 63/Male Blood Icotinib EGFR p.L858R (EX21),CHEK2 c.445-1G>A Combined gefitinib and bevacizumab SD 6+ 7 79/Male Tissue No EGFR p.L747_T751del (EX19), NF1 c.587-1G>C, ATM c.2124+1G>T Gefitinib PR 2+ 8 80/Female Pleural effusion Gefitinib EGFR p.L858R (EX21), EGFR p.T790M (EX20), EGFR amplification Osimertinib PR 7+ 9 81/Male Tissue No EGFR p.G719A (EX18), MET amplification, CDK4 amplification Icotinib SD 4
NGS-based genetic testing comprehensively predicts the effectiveness of targeted therapy. It can be widely used in routine clinical practice.
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