This study evaluates the efficacy and safety of PD-1 and EGFR dual-target neoadjuvant therapy in locally advanced head and neck squamous cell carcinoma, demonstrating favorable antitumor activity and manageable toxicity profile.
Literature Overview
This study, titled 'Neoadjuvant tislelizumab with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-1): a phase 2 clinical trial' published in Nature Communications, systematically reviews the application of PD-1 inhibitor tislelizumab combined with EGFR tyrosine kinase inhibitor afatinib as neoadjuvant therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The research primarily assesses key endpoints including major pathological response rate (MPR) and pathological complete response rate (pCR), while analyzing safety profiles, disease-free survival (DFS), and overall survival (OS).
Background Knowledge
Head and neck squamous cell carcinoma (HNSCC) ranks as the seventh most common cancer globally, with approximately 60% of patients presenting with locally advanced disease at diagnosis. The recurrence rate exceeds 40%, with less than 50% five-year survival rate. Neoadjuvant therapy serves as a pre-surgical strategy to reduce tumor burden and enhance surgical success, though its efficacy in HNSCC remains suboptimal. While immune checkpoint inhibitors (ICIs) demonstrate significant therapeutic effects in recurrent or metastatic HNSCC, monotherapy neoadjuvant approaches show limited MPR rates (approximately 8%). Consequently, combination therapies have become a research focus, particularly dual-targeting strategies against PD-1 and EGFR pathways. Existing studies demonstrate potential in advanced HNSCC, but systematic evaluation in neoadjuvant settings is lacking. EGFR overexpression occurs in over 80% of HNSCC cases, correlating with poor prognosis, and its immune regulatory signaling provides theoretical basis for combination therapy.
Research Methods and Experiments
This single-center, open-label phase 2 clinical trial enrolled 25 LA-HNSCC patients. The treatment regimen involved tislelizumab (200mg intravenous on Day 1 and Day 22) combined with afatinib (30mg/day orally for 42 days) as neoadjuvant therapy. Primary endpoint was MPR rate, secondary endpoints included pCR, ORR, DFS, OS, and safety evaluation. Comprehensive multi-omics analyses were conducted, covering PD-L1 expression, tumor mutation burden (TMB), microsatellite instability (MSI), TCR sequencing, multiplex immunofluorescence (mIF), and salivary microbiome sequencing.
Key Conclusions and Perspectives
Research Significance and Prospects
This study represents the first systematic evaluation of PD-1/EGFR dual-target neoadjuvant therapy in LA-HNSCC, demonstrating improved MPR rates with acceptable safety. Future research requires larger multi-center trials to validate survival benefits across broader HNSCC populations. Elucidating the roles of CD8+ T cells and NK cells in immune activation, alongside exploring microbiome predictive potential, will facilitate development of precision oncology strategies.
Conclusion
This study establishes a novel neoadjuvant strategy for LA-HNSCC patients using PD-1 inhibitor tislelizumab combined with EGFR-TKI afatinib. Achieving MPR rate of 35%, pCR rate of 17%, and ORR of 48% with manageable safety, it demonstrates clinical efficacy. Multi-omics biomarker analysis reveals significant increases in CD8+ T cell and CD56+ cell infiltration in MPR patients, suggesting immune activation contributes to therapeutic response. Salivary microbiome profiling identifies distinct microbial composition between MPR and non-MPR groups, indicating potential regulatory roles. Despite no significant associations with PD-L1, TMB, or MSI, findings suggest dual neoadjuvant targeting enhances CD8+ T cell and NK cell infiltration to improve pathological outcomes. Future validation in expanded cohorts and discovery of reliable predictive biomarkers will optimize personalized treatment strategies.
