Abstract 256P
Background
Implementing precision medicine in PDAC has been challenging due to the low frequency of targetable molecular alterations. This study aims to determine the frequency of PIK3CA mutations in PDAC, given the efficacy of targeted treatments for PIK3CA mutations in other solid tumours.
Methods
Data were extracted from the Genomics Evidence Neoplasia Information Exchange (GENIE) Public Database v15.1. The analysis focused on identifying the prevalence of PIK3CA somatic mutations in PDAC and describing the demographics of patients harbouring these alterations. The study also investigated the co-occurrence of other significant mutations. Survival from time of sequencing was estimated using the Kaplan-Meier method.
Results
Among 6640 patients with PDAC, PIK3CA somatic mutations were found in 2.7% (n=182). The majority of these mutations were oncogenic or likely oncogenic, with the most common protein changes being E545K (n=27), E542K (n=23) and H1047R (n=13). The median age at sequencing was 67 years for both PIK3CA mutant and wildtype groups. The prevalence of PIK3CA mutations was 3.1% in females versus 2.5% in males (p=0.11), and the mutation rates across racial groups were 2.8% White, 3.0% Asian, 2.6% Black and 2.6% other (p=0.98). Samples from metastatic sites (3.2%) were more likely than primary sites (2.2%) to harbour PIK3CA mutations (p=0.02; odds ratio 1.47, 95% CI 1.07-2.01). After a median follow-up of 32.4 months, the median survival time from sequencing was 19.1 months for patients with a somatic PIK3CA mutation, compared to 19.0 months for those without (log-rank p=0.85). Co-occurring mutations included KRAS in 82%, TP53 in 62%, and SMAD4 in 28%.
Conclusions
PIK3CA somatic mutations were identified in nearly 3% of patients with PDAC, with similar distribution across age, gender and racial groups, but with a slightly higher prevalence in metastatic samples. The most common protein changes (E545K, E542K, H1047R) are recognised as oncogenic and have shown predictive responses to PIK3CA inhibition. The frequency of PIK3CA mutations is comparable to BRCA1/2 mutations in PDAC. These findings support routine testing for PIK3CA mutations in PDAC to expand therapeutic options and increase eligibility for clinical trials targeting the PI3K/AKT/mTOR pathway.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Sim: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Institutional, Research Funding, Research funding and drug supply to institution only: AbbVie, Bristol Myers Squibb. All other authors have declared no conflicts of interest.