Abstract 2313: Trends in use of neoadjuvant systemic therapy for head and neck squamous cell carcinoma

Abstract Importance: Neoadjuvant systemic therapy, including chemotherapy and immune checkpoint inhibitors, have potential benefits in head and neck squamous cell carcinoma (HNSCC). These potentially include reducing distant metastases, organ preservation, and treatment personalization. KEYNOTE 689 has the potential to change the treatment paradigm; however, trends in the use of neoadjuvant therapy leading up to the publication of this study remain unclear. Objective: To evaluate trends in the use of neoadjuvant systemic therapy in patients with HNSCC from 2015 to 2022. Design, Setting, and Participants: This retrospective, population-based cohort study utilized data from the National Cancer Database (2015-2021) to analyze neoadjuvant systemic and immunotherapy trends in HNSCC. Neoadjuvant treatment was defined as therapy administered at least 8 weeks prior to definitive surgery. Clinical staging and p16 status were assessed using AJCC 8th edition staging for patients diagnosed after 2018. Associations were analyzed using chi-square tests. Main Outcomes and Measures: The primary outcomes were trends in neoadjuvant therapy use and associations with tumor stage, anatomic site, and p16 status. Results: Among 292, 181 patients (216, 048 [74%] male; 76, 133 [26%] female), 922 received neoadjuvant systemic therapy, and 603 received neoadjuvant immunotherapy. Neoadjuvant therapy use began to rise in 2015 with an immunotherapy use rate of 0.078%, peaking at 0.325% in 2019 (a 4-fold increase) and stabilizing at 0.165% in 2022 (a 2-fold increase from 2015). Similarly, overall neoadjuvant chemotherapy use was 0.22% in 2015, 0.44% in 2019, and 0.26% in 2022. Sites with the largest increases in neoadjuvant immunotherapy use were the floor of mouth (3-fold), gums (2.4-fold), and tongue (2-fold). Patients receiving neoadjuvant therapy were significantly more likely to present with stage 4 disease compared to stages 1-3 (58% vs. 27%; P = .0005). p16 positivity rates were comparable between groups (84% vs. 80%; P = .68). Conclusions and Relevance: The use of neoadjuvant immunotherapy increased by 112% from 2015 to 2022, while overall neoadjuvant systemic therapy use rose by 18%. Patients undergoing neoadjuvant therapy were more likely to present with advanced-stage disease. With the upcoming release of KEYNOTE 689, understanding the current trends and treatment approaches for neoadjuvant therapy are crucial. Citation Format: Wesley L. Cai, Vanessa Helou, Angela L. Mazul, Dan P. Zandberg, Matthew E. Spector, Jose P. Zevallos, Robert L. Ferris, Kevin J. Contrera. Trends in use of neoadjuvant systemic therapy for head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2313.