Presentation (CTI)

OBJECTIVES: Introduction: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with over 700,000 cases diagnosed annually. ctDNA, over the last decade, has emerged as a prognostic biomarker. However, data remains limited on its prognostic value in mHNSCC setting. Therefore, we examined ctDNA burden and their association with clinical outcomes in first line (1L) mHNSCC patients.
METHODS: Methods: We retrospectively evaluated GuardantINFORM database for last decade (June2014-June2024) to identify adult mHNSCC patients with 2+ claims during baseline . Index is defined as the first metastatic event post HNSCC diagnosis. Patients with no detectable ctDNA were excluded. Baseline ctDNA (measured by maximum variant allele fraction [MVAF]) was assessed in the first G360 test post index and categorized as low and high by stratifying at median MVAF of 2.1. We compared the mutation profile and 1L time to next treatment (rwTTNT) and overall survival (rwOS) among mHNSCC cohorts.
RESULTS: Results: 266 low ctDNA patients (ctDNA-L) and 246 high ctDNA patients (ctDNA-H ) were included. The patients in both groups had mean age of 64 years with similar gender, smoking status, race, ethnicity and geographical location; however, differ significantly in their comorbidities (p=0.0093). Median rwOS among ctDNA-L was 24.2 months (95% CI 20.4-31.2) while that of ctDNA-H was 22.1 months (95% CI 16.1-26.4), p=0.0115. ctDNA-Ls also showed longer median rwTTNT compared to the ctDNA-Hs [10.4 months (95% CI 8.2-12.9) vs 6.6 months (95% CI 5.9-7.3), p= 0.0011]. PIK3CA E545K was the most common alteration in both the groups but PIK3CA E542K, TP53 R282W and KRAS G12D were enriched among the HCPs.
CONCLUSIONS: Conclusion: Our study demonstrates that gene alteration and clinical outcomes (rwOS/rwTTNT) differs by ctDNA status. Thereby suggesting utility of ctDNA as a potential biomarker to monitor progression and outcomes in mHNSCC patients in clinical practice.