Systemic therapy for head and neck squamous cell carcinoma: Historical perspectives and recent breakthroughs.

OBJECTIVES: Despite dramatic developments in drugs established for other malignancies, historically there have been few novel systemic agents available for the management of head and neck squamous cell carcinoma (HNSCC). However, the last decade has observed increased interest in targeted therapies for HNSCC. In 2006, cetuximab became the first major drug for HNSCC to gain Food and Drug Administration (FDA) approval in 3 decades. Recently, both pembrolizumab and nivolumab gained FDA approval for treatment of recurrent or metastatic HNSCC, and trials for other indications in HNSCC are actively underway. As older agents including cisplatin and 5-fluorouracil continue to play a significant role in the management of advanced HNSCC, an understanding of their legacy is paramount. This historical review is not meant to exhaustively catalog every finding relating to HNSCC systemic therapy, but rather is meant to highlight important advances.

DATA SOURCES: Case series and clinical trials available in the literature.

REVIEW METHODS: Historically significant series and trials evaluating HNSCC systemic therapy were evaluated.

RESULTS: Standard regimens employed today are largely comprised of drugs discovered over 4 decades ago, although a number of recent phase III clinical trials have shown great promise, leading to the adoption of several new chemotherapeutic agents and treatment strategies.

CONCLUSIONS: These findings reinforce the importance of supporting further HNSCC drug discovery as modern treatment strategies using systemic therapy have resulted in measurable improvements in oncologic outcomes. Laryngoscope, 127:2565-2569, 2017.