Aim: To explore the association between TP53 mutation and atezolizumab in non-small-cell lung cancer (NSCLC) patients. Materials & methods: Patients with NSCLC from the POPLAR and OAK studies were included. Kaplan-Meier analysis was performed to detect progression-free survival (PFS) and overall survival (OS). PFS and OS were compared using multivariate Cox regression analysis. Results: OS was significantly longer with atezolizumab compared with docetaxel among TP53/KRAS co-mutant NSCLC patients (hazard ratio [HR]: 0.014; 95% CI: 0.000-0.721). There is no significant OS difference between atezolizumab versus docetaxel for TP53-mutant NSCLC patients (HR: 0.831; 95% CI: 0.473-1.458). There is no significant OS difference between atezolizumab versus docetaxel for KRAS-mutant NSCLC patients (HR: 1.354; 95% CI: 0.528-3.472). Conclusion: PD-L1 inhibitors may bring OS benefits for patients with NSCLC harbored TP53/KRAS co-mutation.
Keywords: KRAS mutation; TP53 mutation; atezolizumab; non-small-cell lung cancer.
Mutations in TP53 have been reported to be the most frequent oncogenic mutations in non-small-cell lung cancer (NSCLC), but there are no favorable targeted therapies. The association between TP53 mutation and atezolizumab in NSCLC patients was explored in this study. Patients with NSCLC from the POPLAR and OAK studies were included. Longer overall survival (OS) was found in TP53-wildtype NSCLC patients treated with atezolizumab compared with those treated with docetaxel. OS benefit of atezolizumab over docetaxel was detected for NSCLC patients only with co-occurrence of TP53 and KRAS mutations. For patients with NSCLC harboring TP53 mutation detected by fluid biopsy, this study provides insights and perspectives into anti-PD-L1 treatment.