1646P - Genomic and prognostic differences in patients with different KRAS mutations in pancreatic cancer

Background

Approximately 90% of pancreatic cancer patients carry KRAS mutations, and about 80% of pancreatic cancer patients are diagnosed at advanced stage with poor efficacy of first-line treatment. Currently, several anti-tumor small molecule drugs targeting KRAS are under clinical investigation. Exploring the genomic and prognostic information of KRAS-mutated patients can help identify suitable pancreatic cancer patients for targeted therapy.

Methods

From 2017 to 2020, a total of 487 tumor samples were collected from pancreatic cancer patients across China. The laboratory Origimed, certified by the College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA), conducted next-generation sequencing (NGS) of 450 cancer-related genes (YUANSU^TM) in Shanghai, China.

Results

In this study, we found that among 487 patients with pancreatic cancer, the percentages of KRAS G12, non-G12 KRAS mutations, and KRAS wild-type were 79.9%, 7.8%, and 12.3%, respectively. Furthermore, we found that pancreatic cancer patients with KRAS mutations were more likely to have TP53 mutations (82.2% vs 78.4% vs 48.3%, p=9.7x10^-8), while BRAF (23.3% vs 2.6% vs 0.5%, p=3.0x10^-11) and CTNNB1 (21.7% vs 5.3% vs 1.3%, p=1.2x10^-8) were more common mutated genes in KRAS wild-type patients. We found that patients with non-G12 mutations had significantly higher TMB than those with G12 mutations and KRAS wild-type (4.1 vs 2.3, p=0.0008), and this group of patients had significantly lower OS after receiving first-line chemotherapy in our cohort (249 days VS 352 days VS NA, p=0.013), but no difference was observed in PFS.

Conclusions

In this study, we elucidated the genomic differences among pancreatic cancer patients with KRAS G12, non-G12, and KRAS wild-type mutations. Furthermore, we found that patients with non-G12 KRAS mutations had lower OS after receiving first-line chemotherapy compared to other patients, and these patients had higher TMB levels.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.