Abstract 169P
Background
Brain metastases (BM) are common in non-small cell lung cancer (NSCLC) and are associated with poor prognosis. Comprehensive genomic profiling (CGP) has revolutionized the treatment paradigm of NSCLC by detecting multiple druggable mutations and potential predictors or prognosticators for survival, like TP53 and tumour mutation burden (TMB). Herein we report the genomic landscape of BM from a territory-wide program in Hong Kong and investigate the association of BM with TP53 and TMB.
Methods
Patients newly diagnosed with non-squamous NSCLC with BM after March 2021 from the seven public oncology centres in Hong Kong were included. CGP was all performed using next-generation sequencing with FoundationOne and clinical data were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between BM and druggable mutations, TP53, TMB. TMB-H was defined ≥10 mutations/Mb.
Results
Overall 432 patients were recruited in the program as of 23 August 2023 with 124 patients (28.7%) with BM overall. Among the BM cohort, 72.2% & 27.8% of patients had performed tissue and liquid CGP respectively. EGFR (34.7%) and KRAS G12C (8.0%) were the commonest driver mutations while TP53 (67.7%) was the most prevalent mutation of any type. Concurrent EGFR and TP53 mutations were detected in 65.1%. TMB-H was found in 29.0% of overall BM patients but of which only in 4.7% (2/43) for EGFR mutated patients. Association between TMB-H and TP53 mutation was found (p<0.001), with 91.6% of TMB-H patients with TP53 mutation. Multivariate analysis showed TMB-H (OR 2.11, p=0.006) but not TP53 (OR 1.55, p=0.07) was significantly associated with BM at initial diagnosis. For the clinical characteristics of BM, TMB-H was associated with oligometastatic BM (≤4 lesions) (OR: 3.08, p=0.03). There was no association with the characteristics of BM and TP53 mutations.
Conclusions
EGFR is the commonest druggable mutation in this cohort and high prevalence of TP53 was found. TMB-H is strongly associated with TP53, the presence of BM and oligometastatic brain disease. The role of TP53 and TMB for risk stratification in BM patients would require further studies to define.
Legal entity responsible for the study
The University of Hong Kong.
Funding
Roche Hong Kong Limited.
Disclosure
All authors have declared no conflicts of interest.