1663P - Role of next-generation sequencing somatic assays in patients with advanced pancreatic cancer

Background

Recently, the use of Next-Generation Sequencing (NGS) somatic assays has increased aiming the identification of potentially targetable molecular alterations for the treatment of advanced malignancies that progressed after standard therapies. Pancreatic cancer (PC) remains a challenging disease, with poor outcomes, for which novel therapeutic strategies, are largely warranted. Nevertheless, the impact of NSG for the treatment and outcomes of this neoplasia is unclear. The aimed to assess the impact of NGS somatic assays for patients (pts) with advanced pancreatic cancer.

Methods

In this cohort, we evaluated pts with advanced PC (metastatic or locally advanced unresectable) treated in a private cancer network from 2014 to 2021. Electronic records were reviewed for data collection. The study endpoints were the pattern of somatic alterations, the frequency of potentially targetable alterations and the use of targeted therapy directed by the NGS somatic assay.

Results

Among 446 pts with advanced PC, 51 underwent a NGS somatic panel; 44 of them had the panel results available and were evaluated in this study. All pts with panel available had at least one somatic alteration. Most pts (95%) had KRAS mutations; the most common were KRAS G12D (52%), KRAS G12V (17%), KRAS G12R (9%), KRAS G12A (7%), and KRAS Q61H (5%). No patient had a KRAS G12C mutation that could be targeted with anti-KRAS G12C agents. Other frequent molecular alterations were found in the following genes: TP53 (52%), CDKN2A/B (41%), SMAD4 (18%), ARID1A (11%), PTEN (7%), and ATM (4%). Two pts had a BRCA2 mutation that was known to be germline. No patient had microsatellite instability-high or high tumor mutational burden. Overall, 11% had potentially drugable alterations. Only one patient (2%) received a treatment guided by the result of the somatic panel, with a median progression-free survival of 1.6 months.

Conclusions

Unfortunately, NGS somatic panel seems to have limited role for the PC treatment nowadays, with few pts receiving treatment guided by the panel. The development of new targeted therapy directed to the most frequently molecular alterations, including KRAS-directed therapy other than KRAS G12C, are urgently needed to improve outcomes.

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.