Abstract B064: Association of different TP53 mutation subtypes with the efficacy of first-line immunotherapy in locally advanced and metastatic lung squamous cell carcinoma

Abstract Background: TP53 mutations are one of the most common genetic variations in lung squamous cell carcinoma (LUSC), and the heterogeneity of TP53 mutants leads to heterogeneity in clinical outcomes. This study aimed to explore the clinical relevance of specific TP53 mutations in LUSC and improve risk stratification by distinguishing specific TP53 mutations. Methods: We retrospectively reviewed the clinical data of patients with locally advanced or metastatic lung squamous cell carcinoma(199 ) who received first-line immunotherapy at Shanghai Chest Hospital. TP53 mutations were identified by next-generation sequencing (NGS), and we classified TP53 mutations into two categories based on the predicted degree of protein structure disturbance in p53-DNA complexes: disruptive and nondisruptive. In this study, Finally, the association between TP53 mutations and their different subtypes and the efficacy of first-line immunotherapy was analyzed. Results: The median progression-free survival (PFS) of the TP53 disruptive mutation group was 15.27 months[95% CI : 6.83–14.33], and that of the non-disruptive group was 7.93 months[95% CI : 9.77–30.33] (p = 0.008). The objective response rates (ORR) of the two groups were 69.2% and 60.7% (p = 0.41), respectively, and the disease control rates (DCR) were 92.3% and 98.8% (p = 0.07) respectively. Multivariate analysis of PFS showed that TPS ≥ 50% was an independent prognostic factor for patients with lung squamous cell carcinoma receiving first-line immunotherapy. Conclusion: Patients with locally advanced or metastatic squamous cell lung cancer accompanied by TP53 mutations are more likely to benefit from first-line immunotherapy. This work was funded by National Natural Science Foundation of China (82202924 to Y.Y.)and(82030045 to S.L.) Citation Format: yingyun liang, ying yang, shun lu. Association of different TP53 mutation subtypes with the efficacy of first-line immunotherapy in locally advanced and metastatic lung squamous cell carcinoma [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B064.