Abstract 1423P
Background
Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide, however, large aggregated RWD of patients (pts) with advanced gastric cancer (AGC) are not well known. In particular, genomic information is lacking in cancer pts of adolescents and young adults.
Methods
CGP was performed at Foundation Medicine on pts with RWD tested during the course of routine clinical care. Hybrid capture was carried out on up to 395 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. 4,634 pts were available for analyses and were stratified by age (≥40/<40), MSI status, tumor mutational burden (TMB) status (High 10≥/Low <10Muts/Mb), EBV status, and select gene alterations. Using a chi-square test with Yate’s correction, frequencies of genomic alterations were analyzed according to clinical or genomic background.
Results
Genes with frequent alterations included TP53 (60.1%), ARID1A (19.6%), CDKN2A (18.2%), KRAS (16.6%), and CDH1 (15.8%). CGP according to age, MSI, TMB, and ERBB2 amplification is shown in the table. Table: 1423P
| Total | Age | MSI | TMB | ERBB2 amp | |||||||||
| <40 | ≥40 | P-value | High | Non-High | P-value | High | Low | P-value | Pos | Neg | P-value | ||
| N | 4634 | 405 | 4229 | 224 | 4410 | 436 | 4198 | 425 | 4209 | ||||
| TP53 | 60.1% | 62.7% | 59.8% | 0.28 | 45.1% | 60.8% | <0.001 | 56.7% | 60.4% | 0.14 | 82.6% | 57.8% | <0.001 |
| ARID1A | 19.6% | 13.6% | 20.2% | 0.0018 | 75.0% | 16.8% | <0.001 | 48.2% | 16.6% | <0.001 | 8.7% | 20.7% | <0.001 |
| CDKN2A | 18.2% | 14.3% | 18.6% | 0.040 | 13.8% | 18.4% | 0.0076 | 17.7% | 18.3% | 0.80 | 18.1% | 18.2% | 0.99 |
| KRAS | 16.6% | 12.6% | 17.0% | 0.029 | 40.2% | 15.4% | <0.001 | 30.3% | 15.2% | <0.001 | 5.6% | 17.7% | <0.001 |
| CDH1 | 15.8% | 27.7% | 14.7% | <0.001 | 17.4% | 15.7% | 0.56 | 13.1% | 16.1% | 0.11 | 7.3% | 16.7% | <0.001 |
| PIK3CA | 11.9% | 8.4% | 12.2% | 0.028 | 47.3% | 10.1% | <0.001 | 33.9% | 9.6% | <0.001 | 8.0% | 12.3% | 0.012 |
| ERBB2 | 12.9% | 13.3% | 12.9% | 0.85 | 17.0% | 12.7% | 0.079 | 17.7% | 12.4% | 0.0024 |
As shown in the table, differences in CGP were observed according to clinical or genomic background. Interestingly, the number of any gene amplifications was lower in MSI-High compared to TMB-High population. In tumors with ERBB2 amplification, amplification of MYC/CCNE1/GATA6 and CDK12 rearrangement were more frequent, while mutations of KRAS/PIK3CA/ARID1A/CDH1 were rarely observed. Statistical differences in the frequency of genomic alterations in several genes such as TP53 (25% vs. 61%), PIK3CA (58% vs. 10%), ARID1A (47% vs. 19%), and CTNNB1 (28% vs. 4%) were observed in EBV-positive tumors compared with EBV-negative tumors (P<0.001).
Conclusions
The RWD revealed the genomic landscape and differences in CGP according to clinical or genomic background in AGC. These findings would help refine and discover new targets for improved cancer therapies in AGC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Yu Sunakawa.
Funding
Has not received any funding.
Disclosure
K. Umemoto: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical. A. Doi: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical. T. Mizukami: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Lilly Japan; Financial Interests, Personal, Invited Speaker: Otsuka; Financial Interests, Personal, Invited Speaker: Asahi Kasei; Financial Interests, Personal, Invited Speaker: Merck Biopharma; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Chugai Pharma; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Japan; Financial Interests, Personal and Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Lilly Japan. N. Izawa: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Japan; Financial Interests, Personal, Invited Speaker: Lilly Japan; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Takeda. J.A. Moore: Non-Financial Interests, Personal, Member: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. E. Sokol: Non-Financial Interests, Personal, Member: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche. Y. Sunakawa: Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb Japan; Financial Interests, Personal, Advisory Board: MSD K.K; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Chugai Pharma; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Yakult Honsha; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Bayer Yakuhin; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Japan; Financial Interests, Personal, Invited Speaker: Lilly Japan; Financial Interests, Personal, Invited Speaker: Merck Biopharma; Financial Interests, Personal, Invited Speaker: Sysmex; Financial Interests, Personal, Invited Speaker: MSD K.K; Financial Interests, Personal and Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Takeda; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharma; Financial Interests, Personal and Institutional, Research Grant: Lilly Japan; Financial Interests, Personal and Institutional, Research Grant: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Otsuka. All other authors have declared no conflicts of interest.