Abstract 365P
Background
TP53 is the most frequently mutated gene in NSCL, and several studies have suggested that somatic mutations in TP53 are associated with poor prognostic. However, the prognostic role of TP53 mutations when detected in liquid biopsy remains poorly defined.
Methods
Patients (pts) with metastatic NSCLC and mutational status determined by circulating tumor DNA next-generation sequencing, diagnosed between September 2017 and April 2021, were included. They were categorized into two groups: TP53 mutated (TP53 MUT) and TP53 wild-type (TP53 WT). Clinical characteristics and overall survival (OS) were compared between the groups. Median OS was estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival between groups. The potential confounding effects of clinical variables were assessed through multivariate analysis using Cox regression.
Results
In total, 99 pts were included. The median (interquartile range) age was 64 (58–73) years, with 71 (71.7%) males, 79 (79.8%) with a history of smoking, and 68 (68.7%) with adenocarcinoma histology. No differences were observed in the number or sites of metastases Regarding treatment, 54 (54%) pts received immunotherapy, 9 (9.1%) received targeted therapy, and 36 (36.4%) were treated with chemotherapy alone during their disease course. Non-synonymous TP53 mutations were observed in 62 (62.6%) pts. TP53 mutations were significantly associated with male sex (odds ratio [OR]=3.17, 95% confidence interval [CI] 1.28–7.85), smoking history (OR=3.24, 95% CI 1.17–8.91), and non-adenocarcinoma histology (OR=2.70, 95% CI 1.02–7.13). After a median follow-up of 56.7 months (95% CI 41.9–71.4), the median OS in the TP53 MUT group was 13.6 months (95% CI 10.3–16.8), compared to 24.4 months (95% CI 18–30.9) in the TP53 WT group (hazard ratio [HR]=1.85, 95% CI 1.16–2.95, p=0.008). Multivariate analysis confirmed that TP53 mutations were independently associated with shorter OS (HR=1.76, 95% CI 1.08–2.86, p=0.021).
Conclusions
Non-synonymous TP53 mutations detected by liquid biopsy are a negative prognostic factor associated with poorer overall survival, independent of the treatment received.
Funding
Has not received any funding
Disclosure
I. Beltrán: Financial Interests, Institutional, Other, Clinical Trial Sub-Investigator: BeiGene, MSD; Financial Interests, Institutional, Other, Clinical trial subinvestigator: merck sharp & Dohme, Roche, Daiichi Sankyo, Gilead Sciences; Other, Personal, Other, Travel and accommodation: Merck, Servier, Eisai. J. Fuentes Pradera: Financial Interests, Institutional, Other: BeiGene, MSD, Roche, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Advisory Role: Gilead, MSD; Financial Interests, Personal, Speaker’s Bureau: Roche, Bristol Myers Squibb, Takeda, AstraZeneca, Pfizer, Sanofi. E.M. Fernandez: Financial Interests, Institutional, Other, Clinical trial sub-investigator: BeiGene, MSD, Roche –Genentech, Daiichi Sankyo, AstraZeneca, Gilead Sciences; Other, Personal, Other, Travel and Accomodations: Pfizer, Merck Serono, Sanofi, Novartis. A. Sanchez Vegas: Financial Interests, Institutional, Other: BeiGene, MSD, Roche, Daiichi Sankyo, AstraZeneca, Gilead; Other, Personal, Invited Speaker: Pfizer. M. Chaves-Conde: Financial Interests, Institutional, Other: BeiGene, MSD, Roche, Daiichi Sankyo, AstraZeneca, Gilead; Other, Personal, Invited Speaker: MSD, Merck, Bristol.