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Liyun Miao
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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: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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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): Liyun Miao
- 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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P1.01-90 - A Pilot Trial Assessing Apatinib Combined with Docetaxel (DTX) as Second-Line Chemotherapy for EGFR Negative Advanced NSCLC) (ID 13105)
16:45 - 18:00 | Author(s): Liyun Miao
- Abstract
Background
Apatinib is a new tyrosine kinase inhibitor against vascular endothelial growth factor receptor 2 and improves outcomes in patients (pts) with metastatic gastric cancer as a third line of treatment. Recently, it has been reported effective as third- or later-line treatment in advanced NSCLC. This prospective study tried to assess the efficacy and safety of apatinib combined with DTX as second-line treatment of EGFR negative NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this open-label single-arm study, pts recived oral apatinib (500mg, p.o. qd) with DTX(60mg/m2，i.v. d1 q3w) as second-line therapy. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the RECIST 1.1. Treatment was continued until disease progression, death, or intolerable toxicity.
4c3880bb027f159e801041b1021e88e8 Result
Between September 2016 and April 2018, 27 pts were enrolled. In 27 pts, there were 23 pts available for efficiency evaluation and 27 pts available for safety evaluation. In the first evaluation of efficacy at one month, computed tomography scan evaluation revealed that partial response (PR) occurred in 7 of 23 pts and other 15 showed stable disease (SD). The median PFS was 4.0667 months (95% CI: 2.5333–6.3333 months). The median OS was 10.5667 months (95% CI: 10.5667– ~ months). The objective response rate(ORR) was 30.43% and disease control rate(DCR) was as high as 95.65 %. Most of the adverse reactions (AEs) were at grade 1 or 2. The grade 3 AEs were hypertension (n=12, 44.44%), hand-foot syndrome (n=3, 11.11%), diarrhea (n=2, 7.41%), mouth ulceration (n=3, 11.11%), thrombocytopenia (n=1, 3.70%). No grade 4 AE or drug-related mortality occurred.
8eea62084ca7e541d918e823422bd82e Conclusion
Apatinib has a potential application prospect in second-line therapy combined with DTX for EGFR negative NSCLC pts. The research team will continue the study.
6f8b794f3246b0c1e1780bb4d4d5dc53
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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: 2
- 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 | Presenting Author(s): Liyun Miao
- 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): Liyun Miao
- 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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