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J. Hu
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P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.07-038 - The Potential Clinical Application of Comprehensive Genomic Profiling in Targeted Therapy and Immunotherapy of Lung Cancer (ID 10467)
09:30 - 09:30 | Author(s): J. Hu
- Abstract
Background:
The comprehensive genomic profiling (CGP) diagnosis initially designed for targeted therapy is finding its way in cancer therapy with immune checkpoint inhibitors. Besides the utility of identifying targets for precision therapy, CGP also measures the tumor mutational burden (TMB) and the microsatellite instability status (MSI), which both are associated with the response to PD-1 blockade immunotherapy.
Method:
Totally FFPE samples from 147 lung cancer patients (median age=58, male vs. female = 80 vs. 67) were subjected to comprehensive genomic profiling (CGP) assay consisting of 450 gene full exons and selected introns. We measured the mutational atlas of cancer related driver genes and calculated the tumor mutational burden (TMB) of total somatic substitutions and indels per megabase after filtering know driver mutations. The MSI status is determined by identifying and scoring multiple mononucleotide repeats which are instable comparing to matched normal control.
Result:
The oncogenic mutation profile of this cohort is consistent as reported with EGFR mutation (N=70, 47.6%), KRAS mutation (N=14, 9.5%), tyrosine kinase fusions (N=8, 5.4%) and EGFR/KRAS wildtype (N=55, 37.4%). We find that the patients with KRAS mutations have significantly high TMB values (median TMB = 10.6) compared to EGFR mutant patients (median TMB = 4.6; p=0.027). The EGFR mutation subset also showed statistically different TMBs comparing to EGFR/KRAS wildtype (median TMB = 8.4; p=0.034). The TK gene fusion subgroup displays intermediate TMB level at 6.5 with no significant difference to other groups. We also found that about 15% of EGFR wildtype lung patients have high TMB (>20) while only around 6% of EGFR mutation cohort exhibits high TMB. Approcimately 10% of the lung patients exhibits MSI-H status. In this cohort, three lung cancer patients with higher TMB showed good responses to PD1/PDL1 inhibitors, and consistently responded in multiple cycles.
Conclusion:
These results show that a comprehensive gene profiling (GCP) assay is informative for assisting two pillar cancer treatments targeted therapy and immunotherapy. We find that a sizable portion of lung cancer patients with KRAS mutation have higher TMB, which indicated the patients previously lack effective treatments might benefit from cancer immunotherapy. In addition, about 6% of the EGFR mt lung cancer patients might be alternatively treated with immune checkpoint blockade even after the failure of TKI targeted therapy. 10% of lung patients who possesses high MSI score might also suitable for immune checkpoint blockade treatment. However, more samples and investigations are under way.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-018 - Genomic Profiling of Driver Gene Mutations in 498 Chinese NSCLC Patients (ID 10433)
09:30 - 09:30 | Author(s): J. Hu
- Abstract
Background:
Identifying genomic alterations of actionable driver genes in non-small cell lung cancer (NSCLC) such as EGFR, ALK, ROS1 has been used as important evidences for firstline treatments. Patients with driver mutations received matched target drugs could have significantly longer progression free and overall survival.
Method:
FFPE tumor samples of 498 Chinese NSCLC patients including 279 males (56%) and 219 females (44%) with a median age of 60 were collected for next-generation sequencing (NGS)-based multi genes panel assay. Genomic alterations including single base substitution, short and long insertions/deletions, copy number variations, and gene rearrangement and fusions in selected genes were assessed.
Result:
Different histological subtypes of adenocarcinoma (417/498, 83.7%), squamous carcinoma (68/498, 13.7%), mixed carcinoma (6/498, 1.2%) and large cell carcinoma (7/498, 1.4%) were included in the Chinese NSCLC cohort. The top ranked genomic alterations in driver genes were EGFR (47.8%), KRAS (10.0%), ALK fusions (8.2%), PIK3CA (7.0%), HER2 (6.2 %), PTEN (3.6%), BRAF (2.6%), MET (3.6%), RET fusions (1.6%), and ROS1 fusions (0.8%), which counts up to 86.9% of the 498 patients with at least one driver mutation. In addition to common driver mutations, rare mutation types such as EGFR-KDD, EGFR-RAD51, AMOTL2-NTRK1 and KIF13A-RET were also detected by deep sequencing assay.
Conclusion:
Our study revealed the landscape of driver gene mutations in 498 Chinese NSCLC patients. Comparing to the largest public NSCLC cohort from Foundation Medicine, mostly Western populations (N=6823, PMID: 27151654), we identified similar frequencies of some driver genes, but more ALK fusions (8.2% vs 3.9%), EGFR mutations (47.8% vs 20.0%) as druggable target genes, and less KRAS mutations (10.0% vs 32.0%) consistent with reported results. Totally 78.7% of the Chinese patietns harbored at least one mutaiton in the 8 core driver genes including EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, or KRAS (vs. 71% in the FMI cohort). Our findings demonstrated that genomic profiling of driver genes in NSCLC showed significant differences among racial or ethnic groups, which indicated different treatment options between Eastern and Western populations.
