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Shiwang Wen
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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
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JCSE01.14 - Higher Prevalence of EGFR Mutations Significantly Correlates with Lower PD-L1 Expression in Chinese Lung Adenocarcinoma (ID 3428)
07:00 - 11:15 | Author(s): Shiwang Wen
- Abstract
Abstract
Background
EGFR mutations are more prevalent in lung adenocarcinoma compared with other non-small cell lung cancer and are more prevalent in East Asians compared with the other populations. At the same time, we observed lower PD-L1 Tumor Proportion Score (TPS) in Chinese lung adenocarcinoma patients (pts) compared with that in Chinese lung squamous cell carcinoma pts and we also observed the proportion of PD-L1 positive (TPS >= 1%) in Chinese lung adenocarcinoma pts was lower than that in other multicenter cohorts. Then we hypothesize that the higher prevalence of EGFR mutations in Chinese lung adenocarcinoma pts correlates with lower PD-L1 expression.
Methods
The Origimed-based lung adenocarcinoma cohort was a retrospective cohort consisted of more than one thousand Chinese lung adenocarcinoma pts who underwent both NGS panel sequencing and PD-L1 immunohistochemistry (IHC) in a College of American Pathologists (CAP) certified and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory during the year 2017 and 2018. Antibodies used in the PD-L1 IHC assay included 28-8 (sample size = 883) and 22C3 (sample size = 158). Tumor Proportion Score (TPS) was applied. All the slides were reviewed by the same senior pathologist. All the EGFR mutations were manually reviewed in Integrated Genomics Viewer for confirmation. After confirmation, each pts was assigned to EGFR positive group or EGFR negative group. Fisher' s exact test and Student' s t-test were applied.
Results
For antibody 28-8, PD-L1 IHC was positive (TPS >= 1%) in 18% (66/370) EGFR positive pts and was positive in 35% (180/513) EGFR negative pts (fisher exact test p value = 1.6e-5). For antibody 22C3, PD-L1 IHC was positive (TPS >= 1%) in 14% (9/64) EGFR positive pts and was positive in 45% (42/94) EGFR negative pts (fisher exact test p value = 3.8e-3). And we observed a significantly lower PD-L1 TPS in EGFR positive pts for both antibodies (t-test p value = 3.5e-11 for PD-L1 antibody 28-8; t-test p value = 6.0e-5 for PD-L1 antibody 22C3).
Conclusion
The observation demonstrated that lower PD-L1 TPS in Chinese Lung Adenocarcinoma pts was significantly correlated with East-Asian-specific high prevalence of EGFR mutations. The observation reassured that EGFR mutation status should be examined simultaneously with PD-L1 IHC in lung adenocarcinoma pts because it was a confounding factor for predicting immunotherapy outcome using PD-L1 TPS. The observation partly explained the generally higher PD-L1 TPS in Chinese lung squamous carcinoma pts compared with that in Chinese lung adenocarcinoma pts.
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-10 - The Landscape of RET Genomic Alterations in Chinese Non-Small Cell Lung Cancer Patients (ID 1262)
09:45 - 18:00 | Author(s): Shiwang Wen
- Abstract
Background
RET is known as a driver gene which accounts for 1-2% in NSCLC. Recently, RET inhibitors such as LOXO-292 and BLU-667 demonstrated promising efficacy in NSCLC and medullary thyroid cancer. The landscape of RET alterations of the Chinese NSCLC population will be explored in this study.
Method
FFPE tumor and matched blood samples of 3433 Chinese NSCLC patients were collected for performing next-generation sequencing (NGS) based targeted panel sequencing. The genomic variants including single nucleotide variations, indels, copy number alterations and gene rearrangements were analyzed. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were calculated and assessed by NGS algorithms.
Result
The patients with RET alterations, including 61 males and 57 females with a median age of 59.5 years, were identified in approximately 3.4% (118/3433) of the Chinese NSCLC cohort. In this study, 58 out of 118 (1.7%) patients, including 21 males and 37 females with a median age of 58 years, harbored RET rearrangements, which is slightly higher than the published data of MSKCC (1.2%). The partner genes of RET rearrangements were identified by NGS, including KIF5B (38/58), CCDC6 (6/58), and other genes (14/58). TP53 was the most common compound gene with RET rearrangements. Two co-existing EGFR mutations, L858R and L861Q, were identified in 2 RET rearrangement patients without previous treatments. Harbored alterations in the cell cycle pathway and in the PI3K/mTOR pathway were found in 15.5% (9/58) and 12.1% (7/58) of patients, respectively. In addition, 8 patients with RET rearrangements had no other co-occurring common cancer gene mutations. Meanwhile, 56 (1.6%) patients carried RET mutations and 5 (0.2%) patients presented RET amplifications. The median TMB of patients with RET alteration was 4.6 muts/Mb, which was exactly the same as all the 3433 patients (4.6 muts/Mb). Interestingly, patients with RET rearrangements had lower TMB (2.3 muts/Mb, 0-16.2 muts/Mb). All patients with RET alternations were microsatellite stable (MSS).
Conclusion
This is the first study to reveal RET genomic profiling in a large Chinese NSCLC cohort. RET rearrangements were found in 1.7% of Chinese NSCLC. Besides the most common partner genes, 14 RET rearrangements (24%) with uncommon or novel partner genes were identified by NGS. TMB of the patients with RET rearrangements was relatively lower.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-32 - Higher Prevalence of EGFR Mutations Significantly Correlates with Lower PD-L1 Expression in Chinese Lung Adenocarcinoma (Now Available) (ID 191)
10:15 - 18:15 | Author(s): Shiwang Wen
- Abstract
Background
EGFR mutations are more prevalent in lung adenocarcinoma compared with other non-small cell lung cancer and are more prevalent in East Asians compared with the other populations. At the same time, we observed lower PD-L1 Tumor Proportion Score (TPS) in Chinese lung adenocarcinoma patients (pts) compared with that in Chinese lung squamous cell carcinoma pts and we also observed the proportion of PD-L1 positive (TPS >= 1%) in Chinese lung adenocarcinoma pts was lower than that in other multicenter cohorts. Then we hypothesize that the higher prevalence of EGFR mutations in Chinese lung adenocarcinoma pts correlates with lower PD-L1 expression.
Method
The Origimed-based lung adenocarcinoma cohort was a retrospective cohort consisted of more than one thousand Chinese lung adenocarcinoma pts who underwent both NGS panel sequencing and PD-L1 immunohistochemistry (IHC) in a College of American Pathologists (CAP) certified and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory during the year 2017 and 2018. Antibodies used in the PD-L1 IHC assay included 28-8 (sample size = 883) and 22C3 (sample size = 158). Tumor Proportion Score (TPS) was applied. All the slides were reviewed by the same senior pathologist. All the EGFR mutations were manually reviewed in Integrated Genomics Viewer for confirmation. After confirmation, each pts was assigned to EGFR positive group or EGFR negative group. Fisher' s exact test and Student' s t-test were applied.
Result
For antibody 28-8, PD-L1 IHC was positive (TPS >= 1%) in 18% (66/370) EGFR positive pts and was positive in 35% (180/513) EGFR negative pts (fisher exact test p value = 1.6e-5). For antibody 22C3, PD-L1 IHC was positive (TPS >= 1%) in 14% (9/64) EGFR positive pts and was positive in 45% (42/94) EGFR negative pts (fisher exact test p value = 3.8e-3). And we observed a significantly lower PD-L1 TPS in EGFR positive pts for both antibodies (t-test p value = 3.5e-11 for PD-L1 antibody 28-8; t-test p value = 6.0e-5 for PD-L1 antibody 22C3).
Conclusion
The observation demonstrated that lower PD-L1 TPS in Chinese Lung Adenocarcinoma pts was significantly correlated with East-Asian-specific high prevalence of EGFR mutations. The observation reassured that EGFR mutation status should be examined simultaneously with PD-L1 IHC in lung adenocarcinoma pts because it was a confounding factor for predicting immunotherapy outcome using PD-L1 TPS. The observation partly explained the generally higher PD-L1 TPS in Chinese lung squamous carcinoma pts compared with that in Chinese lung adenocarcinoma pts.
