51P Exploring the prognostic value of TP53 mutation in NSCLC in the era of precision oncology: A prospective real-world study

TP53 is one of the most frequently mutated genes in non-small cell lung cancer (NSCLC) and has been associated with a worse prognosis. However, in the era of precision oncology, the prognostic value of TP53 co-mutation with other oncogenic genes remains controversial. Our study aimed to investigate the prognostic value of TP53 mutations in patients with advanced NSCLC. Patients diagnosed with advanced NSCLC after March 2021 from seven public oncology centres in Hong Kong were enrolled and underwent FoundationOne next-generation sequencing prior to treatment. Relationship between TP53 mutation status and progression-free survival (PFS) or overall survival (OS) were analysed using survival analyses. Patients were further subdivided according to the presence of "druggable" or "non-druggable" co-mutations. The impact of using precision oncology-guided first-line treatment in the druggable population on survival was also assessed. A total of 426 patients with advanced NSCLC were included in this study. 244 (57%) harboured TP53 mutations (TP53 mt+) and 182 (42%) were TP53 wild-type (TP53WT). TP53 mt+ had a statistically significant worse PFS (hazard ratio (HR) 1.36; p=0.05) and OS (HR 1.47; p=0.04) when compared with TP53WT cohort. Furthermore, TP53mut+ with non-druggable targets had the worst survival outcomes, compared to TP53mut+ with druggable targets and TP53WT groups: 2-year PFS rate (18.3%, 35.1% and 37.8% respectively; p=0.033) and 3-year OS rate (12.5%, 66.7% and 57.1% respectively; p<0.001). Nevertheless, patients with TP53mt+ and druggable targets who received precision-oncology guided treatments had significantly better PFS (HR 0.50; p=0.01) and OS (HR 0.15; p<0.001) than those who did not. Patients who had EGFR or KRAS mutations receiving targeted first-line therapy had no significant difference in PFS or OS irrespective of TP53 status. TP53mt+ imposes a negative impact on survival in patients with advanced NSCLC. However, this poor prognostic factor becomes negated in patients with druggable targets who receive targeted first-line therapy. Our study further highlights the importance of using precision-directed oncology treatment from the outset.