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Thanyanan Reungwetwattana
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IS09 - Industry Symposium Sponsored by Pfizer Oncology: Expert Question Time: ALK+ NSCLC (ID 286)
- Event: WCLC 2020
- Type: Industry Symposium
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 13:00 - 14:00, Industry Symposia Auditorium (via Industry Hub)
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IS09.02 - Navigating Recent Clinical Data for ALK + TKIS (ID 4346)
13:00 - 14:00 | Presenting Author(s): Thanyanan Reungwetwattana
- Abstract
Abstract not provided
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MA01 - Novel Systemic Treatment in NSCLC (ID 102)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 11:45 - 12:45, Scientific Program Auditorium
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MA01.01 - Chair (ID 4155)
11:45 - 12:45 | Presenting Author(s): Thanyanan Reungwetwattana
- Abstract
Abstract not provided
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P35 - Pathology - Genomics (ID 105)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P35.18 - Genomic Alteration Profiles in Rare Types of Lung Cancer (ID 1471)
00:00 - 00:00 | Author(s): Thanyanan Reungwetwattana
- Abstract
Introduction
The uncommon type of lung cancer is known to have a poor prognosis because of diagnostic difficulty and lack of efficient treatment. Next generation sequencing (NGS) is extensively used for molecular diagnosis and helps guiding cancer treatment in precision medicine era. Our study reported a case series of rare types of lung cancer and the result of NGS profile.
Methods
We enrolled patients with rare types of lung cancer in Ramathibodi hospital from year of 2014 to 2019 and performed genomic testing by FoundationOne CDx NGS platform from tissue specimens.
Results
There were four cases of pleomorphic carcinoma, two cases of hepatoid adenocarcinoma, one case of pulmonary blastoma and pulmonary enteric carcinoma. The NGS results were shown in Table 1.
Case number
Gender/age
Diagnosis
Smoking
Stage
Biomarker finding
Gene Alterations
Overall survival
(months)
Microsatellite status
TMB (mut/mb)
1
M/58
pleomorphic carcinoma
n/a
IV
Stable
Low(4 mut/mb)
KRAS,CSF1R,DNMT3A,
0.6
2
M/82
pleomorphic carcinoma
YES
IIA
Stable
Intermediate
(11 mut/mb)
TP53,MET,NF1,INPP4B
7.3
3
M/77
pleomorphic carcinoma
YES
IIIA
Stable
Intermediate
(13 mut/mb)
TP53,KRAS,CSF1R ,SMO
3.5
4
M/56
pleomorphic carcinoma
YES
IA3
Cannot determined
Intermediate
(13 mut/mb)
TP53,FBXW7,RB
31.2
5
M/52
hepatoid adenocarcinoma
NO
IIIA
Stable
Intermediate
(6 mut/mb)
EGFRdel19,MCL1,NOTCH2
22.8
6
M/58
hepatoid adenocarcinoma
YES
IV
Stable
Intermediate
(9 mut/mb)
STK11
5.2
7
M/39
pulmonary blastoma
YES
IIB
Stable
Low(3 mut/mb)
CTNNB1
32.3
8
F/68
Pulmonary enteric carcinoma
NO
IIIB
Stable
Low(3 mut/mb)
KRAS,TP53,APC,MSH6
16.4
The NGS results from pleomorphic carcinoma of lung showed TP53 mutation (75%) and KRAS mutation (50%). Thus TP53 is probably a common gene alteration in pleomorphic carcinoma. A patient with hepatoid adenocarcinoma (Case number 5) demonstrated EGFR exon 19 deletions and MCL amplification, which had been reported in both lung adenocarcinoma and hepatocellular carcinoma in the previous literature. In addition, another type of rare lung cancer in one of our patient, pulmonary blastoma, the NGS reported CTNNB1 mutation which was also mentioned in the previous report that CTNNB1 mutation was one of the common mutations in pulmonary blastoma. The patient number 8 was very interesting. She had pulmonary enteric adenocarcinoma which tissue IHC showed positive CK20, CDX2, and negative CK7 and TTF1. She also had KRAS, APC, and MSH6 mutation. The PET/CT showed irregular border mass at RUL consistent with primary lung cancer, but all histology and molecular profiles trend to support colorectal cancer. We had started to treat her with lung cancer chemotherapy regimen without any responses then we switched to 5-FU-based regimen with partial response until now.
Furthermore, we also reported predictive biomarkers for immune checkpoint inhibitor which were MSI and tumor mutation burden (TMB). All cases had stable MSI except case number 4 whom had insufficient tissue. Most of patients had low and intermediate TMB in this study.
Conclusion
We don’t know much about molecular profile data in rare types of lung cancer. However, NGS testing may help identifying potential target genes and provide new therapeutic options for this group of patients. The pooled-data from all regions of the world will be very useful for gathering all information to develop the novel treatment.
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P37 - Pathology - Biomarker Testing (ID 107)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P37.22 - Unique Characterization of KRAS Mutation in Non-Small Cell Lung Cancer in Thai Population (ID 3460)
00:00 - 00:00 | Author(s): Thanyanan Reungwetwattana
- Abstract
Introduction
KRASmutations were considered as poor prognostic marker and non-targetable until the recent development of AMG-510, an inhibitor specific for KRASG12Cmutation. Thus, in this study, we aimed to characterize the clinical and molecular characteristics between KRASG12Cand non- KRASG12Cpopulations using NGS.
Methods
Tissue archives of stage I-IV NSCLC patients during 2012 and 2015 were retrieved for DNA extraction. Samples were then analyzed by NGS with Qiagen GeneRead Human Lung Cancer Panel 45 on Ion Torrent system. Variants from NGS with coverage of higher than 1000X and ≥ 3% alternate variant frequency were considered as positive. The cutoff point was validated by Real- time PCR. Clinical data were collected for survival analysis.
Results
Of the 159 FFPE samples, 45 (28.3%) harbored KRASmutations. Eleven (24.4%) of the KRAS-mutant samples were G12C(Table 1) and 34 (75.6%) werenon-G12C. The median age of patients with KRASG12Cand non-KRASG12Cwere 61.5 and 64 years old, respectively. KRASG12Cwas significantly associated with tobacco consumption (P=0.027) and tended to occur more in male (P=0.07) (Table 2). Interestingly, the non-G12C population was significantly associated with the presence of other co-driver mutations such as AKT1, EGFR, andMET, in which, EGFRwas the most prevalent, comprising 61.8 % (n=21) of the population. No significant survival differences (both progression-free survival and overall survival) were found between KRASG12Cand non-KRASG12C.
Table 1: Baseline Clinical Characteristics of 11 patients with KRASG12Cmutation
ID
Age
(yrs)
Sex
Stage at diagnosis
Smoking
Co-mutated gene
Treatment
Status
OS (mo)
KRAS
BRAF
EGFR
Early
palliative
1
50.2
F
T1bN0M0
IA
never smk
G12C G12D Q61R
V600E
del19
-
alive
2
44.6
F
T1aN0M0
IA
never smk
G12C
neg
neg
-
alive
3
29.7
F
T2bN0M0
IIA
never smk
G12C G12D
neg
neg
Cis/vnb
alive
4
73.3
M
T2aN2M0
IIIA
ex-smk
G12C
neg
neg
-
alive
5
75.8
M
T4N2M0
IIIB
ex-smk
G12C
neg
neg
Cb/pem
Gefitinib
Dead
17.2
6
71.4
M
T4N3M0
IIIB
ex-smk
G12C
neg
neg
Cb/pem
alive
7
54.8
M
TxN3M1
IV
current smk
G12C
neg
neg
-
Dead
3.5
8
71.1
M
T3N3M1
IV
current smk
G12C
neg
neg
Cb/pem
Dead
22.1
9
66.8
M
T3N0M1
IV
ex-smk
G12C
neg
neg
Cb/pac
Dead
27.2
10
72.9
M
T3N2M1
IV
ex-smk
G12C
neg
neg
Cb/pac
Loss f/u
11
67.6
M
T4N3M1
IV
ex-smk
G12C
neg
neg
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Dead
0.7
Table 2: Baseline Characteristic of KRASmutation Patients
ConclusionCharacteristics
(n, %)
Total
(n=45)
KRAS subtype
p-value
G12C
(n=11)
non-G12C
(n=34)
Mean age ± SD, yrs
63.5 ± 12.0
61.6 ± 14.8
64.1 ± 1.9
0.567
Gender
0.069
Male
22 (48.9)
8 (72.2)
14 (41.2)
Female
23 (51.1)
3 (27.3)
20 (58.8)
Stage at diagnosis
0.417
0
1 (2.2)
0 (0)
1 (2.9)
I
16 (35.6)
2 (18.2)
14 (41.2)
II
5 (11.1)
1 (9.1)
4 (11.8)
III
6 (13.3)
3 (27.3)
3 (8.8)
IV
17 (37.8)
5 (45.5)
12 (35.3)
Smoking status
0.027
Never-smoker
26 (57.8)
3 (27.3)
23 (67.7)
Ex-smoker
16 (35.5)
6 (54.5)
10 (29.4)
Current smoker
3 (6.7)
2 (18.2)
1 (2.9)
Co-mutation
AKT1
6 (13.3)
0 (0)
6 (17.6)
0.311
BRAF
6 (13.3)
1 (9.1)
5 (14.7)
1.000
EGFR
22 (48.9)
1 (9.1)
21 (61.8)
0.004
MET
5 (11.1)
0 (0)
5 (14.7)
0.313
PIK3CA
1 (2.2)
0 (0)
1 (2.9)
1.000
ROS1
2 (4.4)
0 (0)
2 (5.9)
1.000
No. of mutated gene
0.002
1
19 (42.2)
10 (90.9)
9 (26.5)
2
13 (28.9)
0 (0)
13 (38.2)
3
10 (22.2)
1 (9.1)
9 (26.5)
4
3 (6.7)
0 (0)
3 (8.8)
We identified that G12C subgroup was associated with smoking and the absence of other actionable co-mutations. Longer survival was associated with the presence of EGFRco-mutation, possibly due to the EGFR-TKI. KRASG12Cmutation is one of the crucial oncogenic driven mutations which would effects the survival outcomes. Promising targeted therapy will be useful for treating this group of patient.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.39 - Acquired Resistance Mechanisms in T790M-Positive Advanced NSCLC Tested by Non-Invasive Molecular Testing (NIMT) and Their Clinical Relevance (ID 1803)
00:00 - 00:00 | Author(s): Thanyanan Reungwetwattana
- Abstract
Introduction
There is currently limited knowledge of resistant mechanisms after failure of Osimertinib treatment in T790M-positive NSCLC in Asia. We used Non-Invasive Molecular Testing (NIMT) to explore the acquired resistant mechanisms to Osimertinib and their clinical relevancies.
Methods
This study was performed from January 2016 to December 2019 in T790M-positive NSCLC patients who received Osimertinib after failure of 1st/2nd generation EGFR-TKI treatment in Ramathibodi Hospital lung cancer database. We included patients who had plasma samples before treatment and at disease progression. The paired plasma samples were analyzed for resistant mechanisms by NGS (Thermofisher Pancancer 52 genes) then correlated with clinical outcomes.
Results
The 100 plasma samples from 50 patients were included (17 Males; 33 Females). The median age was 63.5 year-old. The majority of patients were non-smoker (82%) and adenocarcinoma (98%). Types of preexisting mutations were exon 19 deletion (60%), and exon 21 L858R (32%). Most of the patients used Osimertinib as 2nd-line treatment (68%). The response rates were 52% PR, 34% SD, and 14% PD. Nineteen patients (38%) developed more than one resistant alteration. The T790M-loss was most commonly found (50%), followed by PIK3CA (14%), EGFR C797S / HER2 / FGFR2 mutation (10% of each mutation) and EGFR (L792F, P848L/Q)/ BRAF/ RET/ KIT mutation (8% of each mutation), MET mutation (6%), MET exon 14 skipping (4%), MET amplification (2%) and small cell transformation (2%), and so on. EGFR C797S was found only in T790M-maintained patients. The median time to treatment failure (TTF) for taking Osimertinib in all patients was 9.3 mo. The patients with T790M-loss tended to have shorter TTF than the patients with T790M-maintained [median TTF 6.0 vs 10.1 months (mo), P=0.21]. Patients who developed T790M-maintained with C797S had tended of shorter OS compared to T790M-maintained without C797S (11.0 vs 15.2 mo). Furthermore, patients with T790M-loss together with other co-mutations had shorter TTF compared to patients with T790M-loss without other co-mutations (4.1 vs. 10.6 mo, adjusted HR 5.38, P=0.07) (Figure1). The patient who had brain metastasis before using Osimertinib significantly related to T790M-loss and patient who developed brain progression was related to BRAF mutation.
Conclusion
There were heterogeneous mechanisms of acquired resistance to Osimertinib in T790M-positive NSCLC. The patient with T790M-loss tended to have poorer survival compared to T790M-maintained patients. C797S and T790M loss with other co-mutation are the important factors affected the survival outcomes in this group of patients.