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Войти в исследования Targeted oncology · 2026
Association of TP53 Truncating Mutations with Time to Treatment Failure after First-Line Chemoimmunotherapy in HER2-Mutant Non-Small Cell Lung Cancer.
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Yoshimura Akihiro, Yoshida Juichiro, Takumi Chieko, Takayama Koichi
Аннотация
BACKGROUND: Biomarkers associated with first-line chemoimmunotherapy outcomes in HER2-mutant non-small cell lung cancer (NSCLC) remain incompletely characterized.
OBJECTIVE: To evaluate whether TP53 truncating mutations are associated with clinical outcomes after first-line pembrolizumab plus pemetrexed-platinum in patients with HER2-mutant NSCLC.
PATIENTS AND METHODS: We conducted a retrospective clinicogenomic study using the nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. Patients with advanced or recurrent HER2-mutant NSCLC who received first-line pembrolizumab plus pemetrexed-platinum were included. The primary endpoint was time to treatment failure (TTF).
RESULTS: Among 69 patients, 21 (30.4%) harbored TP53 truncating mutations. Patients with TP53 truncating mutations had shorter TTF than those without TP53 truncating mutations (median, 6.0 versus 7.6 months; hazard ratio [HR], 1.97; 95% confidence interval [CI] 1.11-3.49; log-rank P = 0.018). The 9-month TTF rates were 4.8% and 40.6%, respectively. After adjustment for age, Eastern Cooperative Oncology Group performance status, and programmed death-ligand 1 tumor proportion score, TP53 truncating mutations remained associated with shorter TTF (HR, 1.98; 95% CI 1.08-3.63; P = 0.026). No significant differences were observed in overall survival or objective response rate.
CONCLUSIONS: TP53 truncating mutations were associated with shorter TTF during first-line pembrolizumab plus pemetrexed-platinum in HER2-mutant NSCLC, without significant differences in overall survival or objective response rate. These findings suggest a potential association with shorter treatment durability and require validation in independent cohorts.
OBJECTIVE: To evaluate whether TP53 truncating mutations are associated with clinical outcomes after first-line pembrolizumab plus pemetrexed-platinum in patients with HER2-mutant NSCLC.
PATIENTS AND METHODS: We conducted a retrospective clinicogenomic study using the nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. Patients with advanced or recurrent HER2-mutant NSCLC who received first-line pembrolizumab plus pemetrexed-platinum were included. The primary endpoint was time to treatment failure (TTF).
RESULTS: Among 69 patients, 21 (30.4%) harbored TP53 truncating mutations. Patients with TP53 truncating mutations had shorter TTF than those without TP53 truncating mutations (median, 6.0 versus 7.6 months; hazard ratio [HR], 1.97; 95% confidence interval [CI] 1.11-3.49; log-rank P = 0.018). The 9-month TTF rates were 4.8% and 40.6%, respectively. After adjustment for age, Eastern Cooperative Oncology Group performance status, and programmed death-ligand 1 tumor proportion score, TP53 truncating mutations remained associated with shorter TTF (HR, 1.98; 95% CI 1.08-3.63; P = 0.026). No significant differences were observed in overall survival or objective response rate.
CONCLUSIONS: TP53 truncating mutations were associated with shorter TTF during first-line pembrolizumab plus pemetrexed-platinum in HER2-mutant NSCLC, without significant differences in overall survival or objective response rate. These findings suggest a potential association with shorter treatment durability and require validation in independent cohorts.