Prognostic effects of TP53 variants co-occuring in patients with HER2-mutated non-small cell lung cancer (NSCLC).

Abstract

e21065 Background: TP53 variants are common in NSCLC and have been reported as prognostic of poor outcome. The impact of TP53 variants in ERBB2/HER2-mutated NSCLC is unclear. Methods: A total of 40 patients with HER2-mutated NSCLC at Princess Margaret Cancer Centre were identified retrospectively; next generation sequencing results were reviewed for TP53 variant status. Associations between TP53 status with patient and tumor characteristics, and outcomes (overall survival [OS] and progression-free survival [PFS]), were investigated. Median survival was computed by Kaplan-Meier estimator; differences between groups were assessed via Cox proportional hazards regression. Results: Co-occurring TP53 variants and HER2 mutations were found in 19/40 patients (47.5%). Median age was 64.5 years and most patients were female (65%), never-smokers (74%), and had adenocarcinoma (90%; Table 1). Median OS was 39.3 months (95% CI:31 months – not reached [NR]) in the TP53 wildtype (WT) cohort compared to 20.5 months (95% CI:3.7 months - NR) in the TP53 variant cohort (HR 2.65 (95% CI: 1.09-6.43; p = 0.03). Median PFS was 30.9 months [16.7-59.8] vs 15.9 months [10.2-NR], although not statistically significant (HR 1.86, 95% CI 0.83-4.18; p = 0.13). There was a tendency for presence of brain metastases at any point for those with TP53 variants (38% versus 63%, p = 0.11). Of the 29 de novo stage IV patients, 10 (36%) had first line targeted treatment. The rest had chemoimmunotherapy (29%), chemotherapy (25%) or immunotherapy (11%). Overall response rates were similar to first line palliative treatment (33% vs 38%, p = 1.00). Conclusions: Co-occuring TP53 variants with HER2 mutations are prognostic of shorter OS and PFS in NSCLC, and may be associated with a higher incidence of brain metastases. Our larger validation dataset with ~75 patients will be presented.[Table: see text]