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Updated: May 22, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Mutational Landscape of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Association with Immune
Patricia McCoon1, Ying Wang1, Zhongwu Lai1
1AstraZeneca, Waltham, Massachusetts.
Purpose:
Understanding the mutational landscape of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is important in identifying biomarkers to determine which patients may benefit from immune checkpoint inhibitors (ICI).
Experimental Design:
The HAWK (NCT02207530), CONDOR (NCT02319044), and EAGLE (NCT02369874) studies evaluated R/M HNSCC treatment with durvalumab or durvalumab-tremelimumab. Tumor tissue samples pooled from HAWK/CONDOR (n = 153) and plasma cell-free DNA samples from EAGLE (n = 285) were analyzed to identify somatic alterations and association with survival.
Results:
The mutational landscape was similar in tissue and plasma. Compared with the wild type, TP53 mutations were associated with significantly shorter overall survival (OS; HR; 95% confidence interval) with standard of care (SoC; EAGLE: 2.12; 1.20-3.78) and ICIs (HAWK/CONDOR: 1.49; 1.05-2.12 and EAGLE: 1.44; 0.99-2.10). In EAGLE, patients with TP53 mutations had significantly longer OS with durvalumab-tremelimumab versus SoC (P = 0.045). KMT2D mutations were associated with a trend toward longer OS (HR; 95% confidence interval) versus the wild type in HAWK/CONDOR (0.81; 0.56-1.19) and a trend toward longer OS with ICIs versus SoC in EAGLE. For both mutations, a European Cooperative Oncology Group performance status of 1 was associated with worsened OS, and PD-L1 positivity was associated with improved OS.
Conclusions:
This is the first large-scale study to show the mutational landscape of R/M HNSCC and its association with clinical outcomes in patients treated with ICIs or SoC. The TP53 mutation was a negative prognostic marker; however, treatment with durvalumab-tremelimumab significantly improved survival over SoC. Further investigation of KMT2D as a predictive biomarker for immunotherapy in R/M HNSCC is warranted.
