Clinical Impact of TP53 Mutations in Patients with Head and Neck Cancer Who Were Treated with Targeted Therapies or Immunotherapy.

Purpose: TP53 mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial.

Materials and methods: We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: Group 1, alpelisib; Group 2, poziotinib; Group 3, nintedanib; and Group 4, abemaciclib. If there was no identifiable target, the patients were allocated to Group 5 (durvalumab ± tremelimumab).

Results: TP53 mutations were detected in 116/179 patients (64.8%), more frequently in HPV-negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival (PFS) than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in Group 5 (8.1 vs. 33.0 months, p=0.001).

Conclusion: TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.