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EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 13
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.03-01 - Molecular Spectrum of Patients with JAK1 Mutations in East Asian Non-Small Cell Lung Cancer (ID 188)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
JAK1 is a critical effector of pro-inflammatory cytokine signaling and plays important roles in immune function, while abnormal JAK1 activity has been linked to immunological and neoplastic diseases. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring JAK1 mutations.
Method
A total of 933 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of JAK1 mutations and other genes were detected by next generation sequencing.
Result
JAK1 gene mutation rate was 1.50% (14/933) in non-small cell lung cancer, including D660G (2 patients), Q499E (1 patient), L954P (1 patient), C16* (1 patient), R239W (1 patient), S295* (1 patient), I359T (1 patient), E791K (1 patient), Q207L (1 patient), R69H (1 patient), H434Y (1 patient), K218N (1 patient) and E662Q (1 patient), and median overall survival (OS) for these patients was 13.0 months. Among them, all patients were JAK1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=10) co-occurring EGFR mutations had a median OS of 14.5 months and 13.0 months respectively (P=0.70); patients with (n=13) or without (n=1) co-occurring TP53 mutations had a median OS of 15.0 months and 13.0 months respectively (P=0.64); patients with (n=5) or without (n=8) co-occurring KRAS mutations had a median OS of 11.0 months and 15.0 months respectively (P=0.79); patients with (n=3) or without (n=11) co-occurring NF1 mutations had a median OS of 11.0 months and 20.0 months respectively (P=0.11).
Conclusion
Althoght EGFR, TP53, KRAS, NF1 gene accompanied may have less correlation with JAK1 mutation in NSCLC patients, predict which patients may harbor JAK1 mutations, could have implications in triaging toward JAK1 variant identification for potential future targeted therapy. These data have implications for the identification of therapeutic target candidates.
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EP1.03-03 - Association Between Molecular Spectrum of EZH2 Variants and Prognosis in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 93)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
Enhancer of zeste homolog 2 (EZH2) shows upregulated expression in tumors and is an important driver of tumor development and progression. However, the mechanism underlying the mediation of tumor aggressiveness in non-small-cell lung cancer (NSCLC) by EZH2 remains unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring EZH2 mutations.
Method
A total of 1122 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of EZH2 mutations and other genes were detected by next generation sequencing.
Result
EZH2 gene mutation rate was 0.62% (7/1122) in non-small cell lung cancer, including K515R (1 patient), I55M (1 patient), D142H (1 patient), K222N (1 patient), Q66R (1 patient), P486S (1 patient), and S652C (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were EZH2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=5) co-occurring EGFR mutations had a median OS of 16.0 months and 20.0 months respectively (P=0.88); patients with (n=6) or without (n=1) co-occurring TP53 mutations had a median OS of not up to now and 20.0 months respectively (P=0.79); patients with (n=2) or without (n=5) co-occurring BRAF mutations had a median OS of 14.0 months and 20.0 months respectively (P=0.45); patients with (n=2) or without (n=5) co-occurring SMARCA4 mutations had a median OS of 20.0 months and not up to now respectively (P=0.88).
Conclusion
EZH2 mutation may predict a worse prognosis of NSCLC. Methyltransferase inhibitor may be beneficial for NSCLC patients with specific EZH2 mutations. EGFR, TP53, BRAF, SMARCA4 gene accompanied may have less correlation with EZH2 mutation in NSCLC patients. The findings of this study could facilitate both clinical trial design and therapeutic strategies.
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EP1.03-06 - POLD1 Mutations Define a Unique Molecular Class of Non-Small Cell Lung Cancer in Chinese Patients (ID 198)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
Somatic POLE mutations have been found in a subset of non-small cell lung cancer (NSCLC) while POLD1 mutations are reportedly rare in NSCLC. The aim of this study is to investigate mutations and prognosis of NSCLC harboring POLD1 mutations.
Method
A total of 833 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of POLD1 mutations and other genes were detected by next generation sequencing.
Result
POLD1 gene mutation rate was 1.20% (10/833) in non-small cell lung cancer, including L357Rfs*36 (1 patient), R225H (1 patient), D76H (1 patient), I659M (1 patient), T582R (1 patient), A930T (1 patient), A749S (1 patient), G178V (1 patient), V455L (1 patient) and D102N (1 patient), and median overall survival (OS) for these patients was 13.0 months. Among them, all patients were POLD1 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=6) co-occurring EGFR mutations had a median OS of not up to now and 11.0 months respectively (P=0.11); patients with (n=8) or without (n=2) co-occurring TP53 mutations had a median OS of 13.0 months and 12.6 months respectively (P=0.80); patients with (n=2) or without (n=8) co-occurring NRAS mutations had a median OS of 15.0 months and 13.0 months respectively (P=0.61); patients with (n=3) or without (n=7) co-occurring PTPRD mutations had a median OS of not up to now and 13.0 months respectively (P=0.79).
Conclusion
POLD1 mutations represents an uncommon phenotype in NSCLC and may thus reprensent a candidate biomarker for response to immunotherapy in patients with NSCLC.
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EP1.03-07 - Prevalence and Clinicopathological Characteristics of EIF1AX Mutations in Chinese Patients with Non-Small Cell Lung Cancer (ID 127)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
The EIF1AX gene was recently described as a new thyroid cancer-related gene. Its mutations were mainly reported in poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), but also in well-differentiated thyroid cancer (WDTC) and in benign thyroid lesions, although less frequently. The prevalence of these mutations in non-small-cell lung cancer (NSCLC) is unknown. The aim of this study is to investigate mutations and prognosis of NSCLC harboring EIF1AX mutations.
Method
A total of 923 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of EIF1AX mutations and other genes were detected by next generation sequencing.
Result
EIF1AX gene mutation rate was 1.30% (12/923) in non-small cell lung cancer, including D125N (1 patient), G6D (1 patient), R14G (1 patient), G15D (1 patient), W70C (1 patient), K3N (1 patient), G9D (1 patient), R13P (1 patient), R14S (1 patient), R57G (1 patient), G135E (1 patient), and P2L (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were EIF1AX gene with co-occurring mutations. Among them, 11 patients with co-occurring mutations had a median OS of 20.0 months, and OS of one patient without complex mutations was 19.8 months. No statistically significant difference was found between the two groups (P=0.84). Briefly, patients with (n=2) or without (n=10) co-occurring TP53 mutations had a median OS of 14.0 months and 20.0 months respectively (P=0.87); patients with (n=2) or without (n=10) co-occurring STK11 mutations had a median OS of 4.0 months and 20.0 months respectively (P=0.02); patients with (n=3) or without (n=9) co-occurring NRAS mutations had a median OS of 4.0 months and 20.0 months respectively (P=0.17); patients with (n=3) or without (n=9) co-occurring KRAS mutations had a median OS of not up to now and 20.0 months respectively (P=0.88).
Conclusion
There is no significant difference of molecular features in EIF1AX gene mutations in NSCLC. Patients with complex mutations benefited more from therapy than those with single mutations. Next generation sequencing provides a simplified strategy and reasonably high detection rate for EIF1AX mutation, which suggested application of the strategies into clinical molecular diagnostics.
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EP1.03-09 - Epidemiological Study of TSC1 Mutations Among Non-Small Cell Lung Cancer Patients in China (ID 115)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
The tuberous sclerosis complex 1 (TSC1) is an endogenous regulator of the mechanistic target of rapamycin (mTOR). While mTOR has been shown to play an important role in neoplasm. The aim of this study is to investigate mutations and prognosis of NSCLC harboring TSC1 mutations.
Method
A total of 1106 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of TSC1 mutations and other genes were detected by next generation sequencing.
Result
TSC1 gene mutation rate was 1.90% (21/1106) in non-small cell lung cancer, including Q654E (2 patients), R429K (2 patients), A1072D (1 patient), R850S (1 patient), E625K (1 patient), R715Q (1 patient), A84T (1 patient), S1038G (1 patient), M1090I (1 patient), D903H (1 patient), I143N (1 patient), Q3H (1 patient), L134F (1 patient), T1065M (1 patient), V407M (1 patient), S673F (1 patient), D675Y (1 patient), Q149H (1 patient) and T1144P plus L916M (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were TSC1 gene with co-occurring mutations. Briefly, patients with (n=12) or without (n=9) co-occurring TP53 mutations had a median OS of 14.0 months and 15.0 months respectively (P=0.58); patients with (n=9) or without (n=12) co-occurring KRAS mutations had a median OS of not up to now and 14.0 months respectively (P=0.56); patients with (n=2) or without (n=19) co-occurring BRAF mutations had a median OS of 18.5 months and 12.0 months respectively (P=0.71); patients with (n=4) or without (n=17) co-occurring CDKN2A mutations had a median OS of 8.0 months and 18.0 months respectively (P=0.47).
Conclusion
Accompanied gene has not well been connected with TSC1 gene mutations. Our finding expands the mutant spectrum of TSC1 gene and adds new understanding of the phenotype.
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EP1.03-13 - Molecular Characteristics of East Asian Patients with VHL-Mutated Non-Small-Cell Lung Cancer: A Retrospective Study (ID 113)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
The von Hippel-Lindau (VHL) gene is inactivated frequently in sporadic clear-cell renal cell carcinomas (ccRCCs) by genetic alteration. However, the pathological or prognostic significance of VHL gene alteration has not been well defined in the other cancers, especially non-small cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring VHL mutations.
Method
A total of 972 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of VHL mutations and other genes were detected by next generation sequencing.
Result
VHL gene mutation rate was 0.72% (7/972) in non-small cell lung cancer, including W117fs*15 (1 patient), G44A (1 patient), G44V (1 patient), P81S (1 patient), R120T (1 patient), E51K (1 patient) and T100A (1 patient), and median overall survival (OS) for these patients was 22.0 months. Among them, all patients were VHL gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=5) co-occurring EGFR mutations had a median OS of 22.0months and 12.0 months respectively (P=0.16); patients with (n=3) or without (n=4) co-occurring TP53 mutations had a median OS of not up to now and 12.0 months respectively (P=0.23); patients with (n=3) or without (n=4) co-occurring KRAS mutations had a median OS of 3.0 months and 22.0 months respectively (P=0.07); patients with (n=2) or without (n=5) co-occurring SETD2 mutations had a median OS of 3.0 months and 22.0 months respectively (P=0.01).
Conclusion
The present study expanded the database on VHL gene mutations in NSCLC and enriched the spectrum of known somatic mutations of the VHL gene. Chemotherapy may be considered as a possible treatment for carriers of the mutation. SETD2 mutated accompanied mutations might play a poor prognosis in VHL gene mutation NSCLC.
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EP1.03-14 - Clinicopathologic Characteristics and Outcomes of Chinese Patients with Non-Small-Cell Lung Cancer and INPP4B Mutations (ID 109)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumour suppressor in different human cancers. However, the role of INPP4B in the angiogenesis of human non-small cell lung cancer (NSCLC) remains unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring INPP4B mutations.
Method
A total of 750 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of INPP4B mutations and other genes were detected by next generation sequencing.
Result
INPP4B gene mutation rate was 2.80% (21/750) in non-small cell lung cancer, including p.R623K (2 patients), p.N378S (1 patient), p.G187W (1 patient), p.V117I (1 patient), c.1721-1G>T (1 patient), p.R818* (1 patient), p.T829R (1 patient), p.Q753H (1 patient), p.L542M (1 patient), p.I68M (1 patient), p.Q814E (1 patient), p.K448N (1 patient), p.C617F (1 patient), p.Q600H (1 patient), p.G479* (1 patient), p.L155Q (1 patient), p.P572A (1 patient), p.L16V (1 patient), p.F652Y (1 patient), and p.T671S plus p.N228K (1 patient), and median overall survival (OS) for these patients was 15.0 months. Among them, all patients were INPP4B gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=19) co-occurring EGFR mutations had a median OS of 20.0 months and 5.5 months respectively (P=0.01); patients with (n=17) or without (n=4) co-occurring TP53 mutations had a median OS of 15.0 months and 14.4 months respectively (P=0.68); patients with (n=7) or without (n=14) co-occurring PTPRD mutations had a median OS of not up to now and 15.0 months respectively (P=0.48); patients with (n=8) or without (n=13) co-occurring KRAS mutations had a median OS of 17.0 months and 15.0 months respectively (P=0.68).
Conclusion
INPP4B mutations were observed in 2.80 % of cases of NSCLC. INPP4B-mutated NSCLC can exhibit other driver gene alterations. No clinical characteristics were significantly associated with INPP4B mutation.
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EP1.03-17 - Outcomes of Molecular Characteristics in Chinese BAP1-Mutant Non-Small Cell Lung Cancer Patients (ID 140)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
BRCA1-Associated-Protein 1 (BAP1) is a dynamic tumor suppressor which, when mutated, has been associated with an increased risk of uveal melanoma, cutaneous melanoma, mesothelioma, and several other cancers. There is some clinical evidence for the use of BAP1 mutations as prognostic and predictive biomarker. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring BAP1 mutations.
Method
A total of 851 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of BAP1 mutations and other genes were detected by next generation sequencing.
Result
BAP1 gene mutation rate was 1.88% (16/851) in non-small cell lung cancer, including H94Y (1 patient), T177P (1 patient), E198Gfs*45 (1 patient), R238K (1 patient), D34Y (1 patient), Y173C (1 patient), E450K (1 patient), G41C (1 patient), S325F (1 patient), P293L (1 patient), Q28* (1 patient), E498K (1 patient), E631Q (1 patient), H144D (1 patient), Q280* (1 patient), (1 patient) and R518L (1 patient), and median overall survival (OS) for these patients was 24.0 months. Among them, all patients were BAP1 gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=12) co-occurring EGFR mutations had a median OS of 14.5 months and not up to now respectively (P=0.35); patients with (n=9) or without (n=7) co-occurring TP53 mutations had a median OS of not up to now and 24.0 months respectively (P=0.79); patients with (n=3) or without (n=13) co-occurring CDKN2A mutations had a median OS of 24.0 months and not up to now respectively (P=0.57); patients with (n=4) or without (n=12) co-occurring KEAP1 mutations had a median OS of 5.0 months and 24.0 months respectively (P=0.07).
Conclusion
BAP1 genetic alter occurs in a subset of NSCLC, and improved understanding of the implications of BAP1 aberrations is critical for the identification of therapeutic target candidates.
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EP1.03-18 - Analysis of IDH1 Mutation Spectrum from Non-Small-Cell Lung Cancer in East Asian Patients (ID 95)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate. IDH1 mutations are associated with the accumulation of the oncometabolite D-2-hydroxyglutarate, which acts as an epigenetic modifier, and the development of multiple malignancies. Previous studies uncovered mutations in IDH1 in several malignancies, with the most frequent mutation being IDH1 R132H. It has been demonstrated that IDH1 expression is induced in non-small-cell lung cancer (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring IDH1 mutations.
Method
A total of 893 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IDH1 mutations and other genes were detected by next generation sequencing.
Result
IDH1 gene mutation rate was 1.23% (11/893) in non-small cell lung cancer, including Q138S (1 patient), D79V (1 patient), T373N (1 patient), C114* (1 patient), W336L (1 patient), I99M (1 patient), G104R (1 patient), R132C (1 patient), A193S (1 patient), Y34C (1 patient) and H67R (1 patient), and median overall survival (OS) for these patients was 11.0 months. Among them, all patients were IDH1 gene with co-occurring mutations. Briefly, patients with (n=9) or without (n=2) co-occurring TP53 mutations had a median OS of not up to now months and 8.5 months respectively (P=0.32); patients with (n=2) or without (n=9) co-occurring KMT2D mutations had a median OS of 11.5 months and 11.0 months respectively (P=0.80); patients with (n=5) or without (n=6) co-occurring KRAS mutations had a median OS of not up to now months and 8.0 months respectively (P=0.22); patients with (n=2) or without (n=9) co-occurring CREBBP mutations had a median OS of 15.5 months and 8.0 months respectively (P=0.67).
Conclusion
Our results demonstrated that decreased IDH1 gene mutation correlated with poor overall survival in NSCLC patients. IDH1 gene mutation may define a subset of patients with lung cancer appropriate for investigational therapeutic strategies.
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EP1.03-19 - The Frequency and Prognosis of MDM2 Mutations in East Asian Non-Small-Cell Lung Cancer Patients (ID 107)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
In neoplasm, the mouse double minute 2 (MDM2) is an oncoprotein that contributes to the promotion of cell growth, survival, invasion, and therapeutic resistance. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring MDM2 mutations.
Method
A total of 1152 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of MDM2 mutations and other genes were detected by next generation sequencing.
Result
MDM2 gene mutation rate was 0.52% (6/1152) in non-small cell lung cancer, including D179N (1 patient), S84L (1 patient), T195M (1 patient), V234L (1 patient), A471S (1 patient) and E184Q (1 patient), and median overall survival (OS) for these patients was 24.0 months. Among them, all patients were MDM2 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=4) co-occurring EGFR mutations had a median OS of 18.5 months and 24.0 months respectively (P=0.89); patients with (n=4) or without (n=2) co-occurring TP53 mutations had a median OS of 24.0 months and 7.0 months respectively (P=0.05); patients with (n=2) or without (n=4) co-occurring BRCA1 mutations had a median OS of 24.0 months and 13.0 months respectively (P=0.20); patients with (n=2) or without (n=4) co-occurring KEAP1 mutations had a median OS of 15.5 months and 24.0 months respectively (P=0.59).
Conclusion
MDM2 mutations represent a distinct subset of NSCLC. Next generation sequencing showed that MDM2 mutations commonly co-existed with other driver genes. Our results show that MDM2 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through MDM2 inhibition might offer new opportunities.
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EP1.03-24 - Clinicopathologic Characteristics and Survival Outcome in Chinese Patients with Non-Small Cell Lung Cancer and HGF Mutations (ID 137)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
Hepatocyte growth factor (HGF) is the ligand for the tyrosine kinase receptor MET (Mesenchymal Epithelial Transition Factor also known as Hepatocyte Growth Factor Receptor, HGFR). HGF and its receptor, MET, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers, especially non-small cell lung caner (NSCLC). The aim of this study is to investigate mutations and prognosis of NSCLC harboring HGF mutations.
Method
A total of 526 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of HGF mutations and other genes were detected by next generation sequencing.
Result
HGF gene mutation rate was 4.56% (24/526) in non-small cell lung cancer, including E437K (1 patient) , L677I (1 patient), S386L (1 patient), R242Q (1 patient), H717N (1 patient), G520R (1 patient), R234H (1 patient), A713G (1 patient), P703S (1 patient), D264N (1 patient), N127K (1 patient), G506E (1 patient), C84* (1 patient), R647Q (1 patient), G133V (1 patient), D257N (1 patient), S386L (1 patient), S166R (1 patient), P27H (1 patient), C612* (1 patient), W528L (1 patient), G133V (1 patient), G694Wfs*31 (1 patient), and T143S plus G146A (1 patient), and median overall survival (OS) for these patients was 20.0 months. Among them, all patients were HGF gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=20) co-occurring EGFR mutations had a median OS of not up to now and 20.0 months respectively (P=0.18); patients with (n=19) or without (n=5) co-occurring TP53 mutations had a median OS of 20.0 months and 21.0 months respectively (P=0.96); patients with (n=4) or without (n=21) co-occurring BRAF mutations had a median OS of not up to now and 20.0 months respectively (P=0.46); patients with (n=5) or without (n=19) co-occurring ERBB4 mutations had a median OS of 20.0 months and 19.6 months respectively (P=0.83).
Conclusion
EGFR, TP53, BRAF and ERBB4 gene accompanied may have less correlation with HGF mutation in NSCLC patients. Results of ongoing studies will provide a platform for further research to offer individualized therapy with the purpose of improving outcomes.
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EP1.03-28 - Frequency and Molecular Characteristics of BRCA1 Mutations in Non-Small Cell Lung Cancer from East Asian Patients (ID 145)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. The aim of this study is to investigate mutations and prognosis of NSCLC harboring BRCA1 mutations.
Method
A total of 730 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of BRCA1 mutations and other genes were detected by next generation sequencing.
Result
BRCA1 gene mutation rate was 2.60% (19/730) in non-small cell lung cancer, including Y856H (3 patients), M1689T (2 patients), N909I (2 patients), G275D (2 patients), N473S (2 patients), S1217C (1 patient), M1628T (1 patient), E649* (1 patient), R1443* (1 patient), V191I (1 patient), I783V (1 patient), M669T (1 patient), and R71K (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were BRCA1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=16) co-occurring EGFR mutations had a median OS of 20.0 months and 13.0 months respectively (P=0.56); patients with (n=4) or without (n=15) co-occurring TP53 mutations had a median OS of 20.0 months and 19.5 months respectively (P=0.82); patients with (n=4) or without (n=15) co-occurring PIK3CA mutations had a median OS of not up to now and 13.5 months respectively (P=0.36); patients with (n=5) or without (n=14) co-occurring CDKN2A mutations had a median OS of not up to now months and 13.5 months respectively (P=0.28).
Conclusion
Our data reveal BRCA1 mutations represent a distinct subset of NSCLC. NGS might be useful for evaluation of BRCA1 unclassified variants. Our results show that BRCA1 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through PARP inhibition might offer new opportunities.
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EP1.03-35 - Prevalence, Clinicopathologic Characteristics, and Molecular Associations of IGF1R Mutations in East Asian Patients with NSCLC (ID 155)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
IGF1R is a ubiquitous receptor tyrosine kinase that plays critical roles in cell proliferation, growth and survival. Clinical studies have demonstrated upregulation of IGF1R mediated signaling in a number of malignancies including colon, breast, and lung cancers. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer (NSCLC) harboring IGF1R mutations.
Method
A total of 812 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of IGF1R mutations and other genes were detected by next generation sequencing.
Result
IGF1R gene mutation rate was 1.60% (13/812) in non-small cell lung cancer, including N977I (2 patients), S751T (1 patient), E1043D (1 patient), G171W (1 patient), E563K (1 patient), R275C (1 patient), F921[2>1] (1 patient), E712K (1 patient), R222W (1 patient), D1024A (1 patient), A760T (1 patient), and K533N (1 patient), and median overall survival (OS) for these patients was 9.0 months. Among them, all patients were IGF1R gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=10) co-occurring EGFR mutations had a median OS of 6.0 months and 11.0 months respectively (P=0.10); patients with (n=12) or without (n=1) co-occurring TP53 mutations had a median OS of 18.0 months and 8.0 months respectively (P=0.68); patients with (n=4) or without (n=9) co-occurring KRAS mutations had a median OS of 14.5 months and 7.0 months respectively (P=0.76); patients with (n=5) or without (n=8) co-occurring NF1 mutations had a median OS of not up to now and 6.5 months respectively (P=0.24).
Conclusion
EGFR, TP53, KRAS, NF1 gene accompanied may have less correlation with IGF1R mutation in NSCLC patients. We report different mutations than those previously reported, which emphasizes the importance of personalized medicine that could be empowered by the use of bioinformatics tools in the diagnostic process and therapeutic approaches.
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 3
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-45 - ROS1-ADGRG6: A Novel ROS1 Oncogenic Fusion Variant in Lung Adenocarcinoma and the Response to Crizotinib (ID 96)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
ROS1 rearrangements are validated driver genes in non-small cell lung cancer (NSCLC) and have been identified in a small subset (1%-2%) of patients with NSCLC. To date, 18 different fusion genes of ROS1 in NSCLC have been identified. The ALK inhibitor, crizotinib, exhibits therapeutic efficacy against ROS1-rearranged NSCLC. In addition to immunohistochemistry, real-time PCR, and fluorescence in situ hybridization, next-generation sequencing (NGS) technology represents a novel tool for ROS1 detection that covers a wide range of fusion genes.
Method
A 55-year-old female with stage IV was detected with a novel ROS1 fusion afther treated with gefitinib due to detection of an EGFR mutation (L858R). Histological examination was consistent with lung adenocarcinoma.
Result
A NGS assay showed that the tumor had a novel ROS1-ADGRG6 rearrangement generated by the fusion of exons of 1-33 of ROS1 on chr6: q22.1 to exons of 2-26 of ADGRG6 on chr6: q24.2. The predicted ROS1-ADGRG6 protein product contained 3075 amino acids comprising the N-terminal amino acids 1-1853 of ROS1 and C-terminal amino acid 1-1222 of ADGRG6. The patient had a favorable tumor response to crizotinib.
Conclusion
ROS1-ADGRG6 is a novel ROS1 fusion gene in NSCLC detected by NGS and should be considered in ROS1 detection assays.
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EP1.14-46 - The KIF5B-RET Fusion as a Novel Mechanism of Acquired EGFR Tyrosine Kinase Inhibitor Resistance in Lung Adenocarcinoma (ID 103)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
Lung cancer is a common malignancy and a leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. And most NSCLC patients with epidermal growth factor receptor (EGFR) mutations respond well to the treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Unfortunately, almost all patients with effective EGFR-TKIs therapy eventually develop drug resistance in about 1 year. The most common mechanism of acquired resistance to first-generation EGFR-TKI treatment is the development of the T790M mutation in exon 20 of the EGFR, which occurs in almost one half of cases of acquired resistance.
Method
In this case report, we present a 72-year-old male non-smoker patient with an EGFR exon 19 deletion diagnosed with lung adenocarcinoma (LADC), who initially responded to first-generation EGFR-TKI treatment, but developed acquired resistance, and was shown to have gene detected by the next generation sequencing.
Result
Repeated liquid biopsy showed the KIF5B-RET fusion gene by next generation sequencing. Therefore, cabozantinib was added to the treatment, and stable disease (SD) was achieved. Unfortunately, the patient did not acquire long-term benefits and the progression-free survival (PFS) was only 2 months
Conclusion
Our results suggested that the KIF5B-RET fusion gene is a possible novel cause of acquired resistance to first-generation EGFR-TKIs.
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EP1.14-47 - Lung Adenocarcinoma with Concurrent KRAS Mutation and ALK Rearrangement Responding to Crizotinib (ID 108)
08:00 - 18:00 | Author(s): Yong Song
- Abstract
Background
Chromosomal translocation resulting in the fusion between the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene has been considered as a novel oncogenic fusion in a subset of non-small cell lung cancer (NSCLC), mostly in non-smokers with adenocarcinoma. EML4-ALK translocations are commonly reported to be mutually exclusive with EGFR or KRAS mutations.
Method
We reported a rare case of 47-year-old female was diagnosed with lung adenocarcinoma and treated with three cycles of chemotherapy. A biopsy acquired after disease progression revealed concurrent KRAS mutation and ALK translocation by a NGS assay.
Result
Based on molecular findings, treatment was initiated with crizotinib in September, 2016. After 2 months of therapy, the patient achieved a partial response. Afterwards, the patient was further administrated with crizotinib for 9 months with a stable disease before tumor progression.
Conclusion
A further understanding of the molecular biology with multiple oncogenic drivers will promote the optimal treatment for NSCLC.
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MA14 - The Adequate MTarget Is Still the Issue (ID 140)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Diego Signorelli, Juergen Wolf
- Coordinates: 9/09/2019, 15:45 - 17:15, Hilton Head (1978)
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MA14.05 - A Randomized Phase III Trial of Fruquintinib Versus Placebo in Patients with Advanced Non-Small Cell Lung Cancer (FALUCA) (Now Available) (ID 1490)
15:45 - 17:15 | Author(s): Yong Song
- Abstract
- Presentation
Background
Fruquintinib, an orally active kinase inhibitor that selectively targets vascular endothelial growth factor (VEGF) receptor, demonstrated significant benefit in progression-free survival and disease control in a randomized Phase II study in patients with non-small-cell lung cancer (NSCLC) who had failed two lines of chemotherapy. This Phase III FALUCA trial is a randomized, double-blind, placebo-controlled, multicenter trial designed to confirm the efficacy in the same patient population (NCT02691299).
Method
From December 2015 to February 2018, 45 clinical centers across China participated in the trial. A total of 730 patients aged 18-75 with advanced NSCLC who had failed two lines of chemotherapy were screened and 527 who met the eligibility criteria were enrolled into the study. Patients were stratified based on epidermal growth factor receptor mutation status and prior use of VEGF inhibitor therapy, and were randomized in a 2:1 ratio to receive fruquintinib (n=354) or placebo (n=173) once daily in a 3 weeks on/1 week off 4-week cycle. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response. The final data cutoff was on September 21, 2018.
Result
Median OS was 8.94 months for fruquintinib and 10.38 months for placebo (hazard ratio, 1.02; 95% CI, 0.816 to 1.283; p=0.841). Median PFS was 3.68 months for fruquintinib comparing to 0.99 months for placebo, respectively (hazard ratio, 0.34; 95%CI, 0.279 to 0.425; p<0.001). The ORR and DCR were 13.8% and 66.7% for fruquintinib, compared with 0.6% and 24.9% for placebo (both p<0.001), respectively. The most frequent treatment-emergent adverse events with fruquintinib (≥grade 3) were hypertension (20.7%), hand-foot syndrome (11.0%), and proteinuria (1.4%). A sensitivity analysis revealed that median OS was significantly prolonged with fruquintinib compared with placebo in patients who received no subsequent systemic anti-tumor therapies (7.00 months versus 5.06 months ; hazard ratio, 0.64; 95%CI, 0.453 to 0.903; p=0.010).
Conclusion
The FALUCA trial failed to meet the primary end point of OS while confirming significant benefit in secondary end points including PFS, ORR and DCR. The safety profile of fruquintinib in this patient population was acceptable and consistent with that identified in the Phase II study. A post-hoc sensitivity analysis revealed that the anti-tumor therapies that patients received post disease progression probably contributed to the failure of this study on the primary end point.
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OA02 - A New Vision of Targets and Strategies (ID 120)
- Event: WCLC 2019
- Type: Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:Frank Griesinger, Luis Paz-Ares
- Coordinates: 9/08/2019, 10:30 - 12:00, Seoul (2007)
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OA02.03 - The Third Generation EGFR Inhibitor (EGFR-TKI) HS-10296 in Advanced NSCLC Patients with Resistance to First Generation EGFR-TKI (Now Available) (ID 766)
10:30 - 12:00 | Author(s): Yong Song
- Abstract
- Presentation
Background
HS-10296 is an oral, potent, high selective third generation EGFR tyrosine-kinase inhibitor (EGFR-TKI) for sensitizing mutations, and the EGFR Thr790Met (T790M) resistance mutation which has been demonstrated by phase I study. This phase II, open-label, multicenter single-arm study was designed to confirm the efficacy and safety of HS-10296 in a large population of non-small-cell lung cancer (NSCLC) patients with EGFR T790M mutation, who had progressed after first generation EGFR-TKI treatment.
Method
Patients aged at least 18 years with centrally confirmed EGFR T790M-positive mutations, locally advanced or metastatic (stage IIIB/IV) NSCLC after first generation EGFR-TKI treatment received HS-10296 110 mg orally once daily until disease progression, or intolerable toxicity, or patient withdrawal. Patients with asymptomatic, stable brain metastases not requiring steroids were allowed to enroll. The primary endpoint was the objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1 every 6 weeks. Response endpoints (ORR and disease control rate [DCR]) were assessed in response analysis set. Secondary end points including progression-free survival (PFS), duration of response (DoR), depth of response (DepOR), overall survival (OS) and safety were evaluated in full analysis set. The final data cutoff was on Jan 5, 2019. The study is still ongoing.
Result
Totally, 244 patients (median age 60.8) entered study in 36 sites in mainland China (189 patients) and Taiwan (55 patients) between May 16, 2018 to Oct 23, 2018. 2 patients were excluded from the evaluable for response analysis set (n=242) due to absence of measurable disease at baseline by independent central review. At data cutoff, 182 (74.6%) patients remained on treatment. The median duration of follow-up was 4.7 months. 160 of 242 patients achieved confirmed partial responses by independent central review. The ORR was 66.1% (95% CI: 59.8-72.1). The DCR was 93.4% (95% CI: 89.5-96.2). The most common adverse reactions (≥ 10%) were blood creatine phosphokinase increased (43 [17.6%]), aspartate aminotransferase increased (29 [11.9%]), pruritus (28 [11.5%]), rash (28 [11.5%]) and alanine aminotransferase increased (26 [10.7%]). The most common all-causality grade 3 and 4 adverse events were blood creatine phosphokinase increased (14 [5.7%]) and hyponatraemia (4 [1.6%]). Serious adverse events were reported in 30 (12.3%) patients, of which 19 (7.8%) were investigator assessed as possibly treatment-related to HS-10296. Three deaths were due to adverse events; one was related to cardiopulmonary failure, other two events occurred after disease progression. There was no interstitial lung disease during study treatment.
Conclusion
HS-10296 has demonstrated good clinical benefit with minimal toxicity in patients with EGFR T790M-positive NSCLC patients who have progressed after first generation EGFR-TKI treatment. The Phase III study has already launched comparing HS-10296 with gefinitib in advanced NSCLC patients with EGFR sensitizing mutations. (The study was sponsored by Jiangsu Hansoh Pharmaceutical Co., Ltd.; ClinicalTrials.gov number, NCT02981108)
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-19 - Predictive and Prognostic Values of ctDNA Clearance in Osimertinib Treated Advanced Non-Small Cell Lung Cancer Cohort (Now Available) (ID 2061)
09:45 - 18:00 | Presenting Author(s): Yong Song
- Abstract
Background
Although growth advantage of certain clones would ultimately translate into a clinically visible disease progression, radiological imaging does not reflect clonal evolution at the molecular level. Circulating tumor DNA (ctDNA), validated as a tool for mutation detection in lung cancer, reflects dynamic molecular changes. Here, we evaluated the potential of ctDNA in monitoring molecular changes and predicting clinical outcomes of EGFR T790M-positive osimertinib treated NSCLC patients.
Method
This prospective multicenter study, enrolled 72 T790M positive osimertinib-treated advanced NSCLC patients who progressed on prior EGFR-TKI to evaluate the potential of ctDNA in monitoring, is part of the ongoing ASTRIS study (NCT02474355). Longitudinal plasma samples, collected from 52 patients, were subjected to sequencing using a panel consisting of 168 lung cancer-related genes.
Result
Genomic profile prior to the initiation of osimertinib revealed that mutations participating in cell cycle (14 patients, p=0.004) and P53 pathways (43 patients, p=0.032) were associated with shorter OS (p53 was excluded from analysis due to high mutation frequency). Interestingly, patients with undetectable ctDNA at first follow-up (within 50 d, n=41) were correlated with longer PFS (p=0.009) and OS (p=0.022). With a median follow-up of 168 d (ranged from 40 - 550 d), 32 patients experienced radiological disease progression. Among them, 11 (34%) experienced molecular progression reflected by emergency of new mutation or increased allelic frequency of existing mutation prior to radiological progression, with an average leading time of 74 days. Patients with molecular PD prior to radiological PD were more likely to harbor any gene copy number amplification (CNA, p=0.035) and p53 (p=0.023) mutations at radiological PD. In addition, patients with CNA at radiological PD had shorter PFS (p=0.002) and OS (p=0.052).
Conclusion
This clinical trial study demonstrates that ctDNA clearance at first follow-up can serve as a predictive and a prognostic marker for patients undergoing osimertinib treatment. Furthermore, it revealed the potential of ctDNA in early detection of disease progression, preceding imaging modalities with an average lead time of 74 days.
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P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 3
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.03-24 - Thoracic Injection of PD-1 Blocking Antibody Improves the Murine Model of Malignant Pleural Effusion (ID 1497)
09:45 - 18:00 | Author(s): Yong Song
- Abstract
Background
Malignant pleural effusion (MPE) occurs as a common complication of lung cancer with poor prognosis. It should be mainly attributed to pleura metastasis and lymphatic obstruction by cancer cells. Despite that intravenous immune-checkpoint inhibitor (ICIs) shows remarkable therapeutic capacity, the effect of thoracic injection of anti-PD-1 antibodies remains undefined.
Method
MPE xenografts mice model was established by intralumen injection of Lewis lung carcinoma (LLC) cells and randomly divided into three groups: high dose of anti-PD-1 monoclonal antibody (200ug), low dose of anti-PD-1 monoclonal antibody (50ug) and an equal volume of saline. Drugs were injected into the pleural cavity on Day 7 and Day 14. Computed tomography (CT) was performed 14 days after LLC injection. All mice were sacrificed on day 21 and the volume of pleural effusion, the number of pleural nodules were quantitatively recorded. Expression of PD-1, PD-L1, CD8+ and CD31 in tumor and normal pleural tissues were evaluated by western blot and immunohistochemical staining (IHC). Flow cytometry was performed on mice spleen after grinding. Weight and survival were recorded.
Result
The volume of pleural effusion, the number of pleural tumor foci and the proportion of CD8+ T cells in the spleen of mice were significantly reduced in both high and low dose of anti-PD-1 antibody treatment groups. Western Blot results showed that the expression of PD-1 in tumor and adjacent pleura was significantly inhibited after anti-PD-1antibody treatment. IHC results showed that CD8+ T cells in tumor area of mice in high dose anti-PD-1 monoclonal antibody group were significantly less than those in low dose group, and the expressions of PD-1 and PD-L1 were significantly increased. Anti-PD-1 monoclonal antibody treatment was associated with much longer survival (p=0.0098). Median survival in the anti-PD-1 antibody treated group was 39 days, versus 29 days in the control group.
Conclusion
Intralumen delivery of anti-PD-1 antibody could significantly reduce MPE volume and improve survival by inhibiting the expression of PD-1, reducing the number of CD8+ T cells in the tumor region and spleen, and affecting angiogenesis.
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P1.03-35 - Analysis of TET2 Gene Aberrations in East Asian Non-Small-Cell Lung Cancer Patients and Evaluation of Their Prognosis (ID 97)
09:45 - 18:00 | Author(s): Yong Song
- Abstract
Background
Ten-eleven translocation 2 (TET2) enzymes are frequently deregulated in cancer, but the genetic spectrum of TET2 mutation non-small cell lung cancer patients (NSCLC) patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring TET2 mutations.
Method
A total of 895 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of TET2 mutations and other genes were detected by next generation sequencing.
Result
TET2 gene mutation rate was 1.90% (17/895) in non-small cell lung cancer, including G126W (1 patient), E1477* (1 patient), I1871Nfs*4 (1 patient), T665K (1 patient), Y60F (1 patient), D932H (1 patient), M533I (1 patient), R1262W (1 patient), N71Kfs*5 (1 patient), Q769* (1 patient), W1198C (1 patient), Y1645Ifs*16 (1 patient), Q1532* (1 patient), R369W (1 patient), D648Y (1 patient), G1370V (1 patient) and T344K (1 patient), and median overall survival (OS) for these patients was 19.0 months. Among them, all patients were TET2 gene with co-occurring mutations. Briefly, patients with (n=15) or without (n=2) co-occurring TP53 mutations had a median OS of 19.0 months and 4.0 months respectively (P<0.01); patients with (n=3) or without (n=10) co-occurring CTNNB1 mutations had a median OS of 13.0 months and 19.0 months respectively (P=0.90); patients with (n=3) or without (n=10) co-occurring NF1 mutations had a median OS of not up to now months and 13.0 months respectively (P=0.87), patients with (n=3) or without (n=10) co-occurring KDM5C mutations had a median OS of not up to now months and 13.0 months respectively (P=0.75).
Conclusion
TET2 oncogenic activation through mutation defines a novel and distinct subset of NSCLC. CTNNB1, NF1 and KDM5C gene accompanied may have less correlation with KIT mutation in NSCLC patients. TP53 accompanied mutations might play a good prognosis in TET2 gene mutation non-small cell lung cancer.
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P1.03-47 - KEAP1 Mutations in East Asian Patients with NSCLC: An Investigation of Prevalence, Clinicopathologic Characteristics and Prognosis (ID 104)
09:45 - 18:00 | Author(s): Yong Song
- Abstract
Background
The KEAP1/NRF2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far. The aim of this study is to investigate mutations and prognosis of NSCLC harboring KEAP1 mutations.
Method
A total of 317 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of KEAP1 mutations and other genes were detected by next generation sequencing.
Result
KEAP1 gene mutation rate was 10.09% (32/317) in non-small cell lung cancer, including D618Tfs*54 (2 patients), W252L (1 patient), G158C (1 patient), D618Tfs*54 (1 patient), L237Q (1 patient), R415C (1 patient), K97N (1 patient), C368F (1 patient), A95T (1 patient), C273F (1 patient), S243F (1 patient), E149K (1 patient), H96L (1 patient), L70Q (1 patient), G558W (1 patient), E493K (1 patient), A40P (1 patient), E343V (1 patient), E219* (1 patient), G158C (1 patient), D235Tfs*3 (1 patient), I125T (1 patient), R320L (1 patient), R470H (1 patient), E244* (1 patient), G158V (1 patient), C368F (1 patient), I185F (1 patient), N157_M161del (1 patient), R336* (1 patient) and E219Q plus D526N (1 patient), and median overall survival (OS) for these patients was 13.5 months. Among them, all patients were KEAP1 gene with co-occurring mutations. Briefly, patients with (n=20) or without (n=12) co-occurring TP53 mutations had a median OS of 14.5 months and 13.5 months respectively (P=0.71); patients with (n=15) or without (n=17) co-occurring KRAS mutations had a median OS of 15.0 months and 12.0 months respectively (P=0.79); patients with (n=16) or without (n=16) co-occurring STK11 mutations had a median OS of 13.5 months and 18.0 months respectively (P=0.60); patients with (n=4) or without (n=28) co-occurring PIK3CA mutations had a median OS of not up to now and 12.0 months respectively (P=0.16).
Conclusion
KEAP1 gene mutation coexists with other gene mutation in NSCLC. TP53, KRAS, STK11 and PIK3CA gene accompanied may have less correlation with KEAP1 mutation in NSCLC patients. Analysis of KEAP1 mutations shows promise as a way to refine individual patients with NSCLC, and provides more insight into effective treatment strategies for patients with KEAP1 mutations.