Outcomes of neoadjuvant checkpoint inhibitor therapy followed by definitive chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC).

Abstract

e18014 Background: Approximately 70,000 Americans are diagnosed with HNSCC annually. While the KEYNOTE-689 trial established the benefit of neoadjuvant pembrolizumab in surgical candidates, its role in patients transitioning to definitive chemoradiation (CRT) for organ preservation requires further validation. This study evaluates the clinical outcomes, safety, and feasibility of neoadjuvant immune checkpoint inhibitor (ICI) therapy ± platinum/taxane-based chemotherapy in patients with locally advanced (LA) HNSCC undergoing definitive CRT. Methods: We conducted a retrospective cohort analysis of patients with LA-HNSCC at Mount Sinai Hospital. Inclusion criteria: new malignancy treated with 2–3 cycles of neoadjuvant ICI ± chemotherapy followed by definitive CRT (standard cisplatin/carboplatin with concurrent radiation). The primary endpoint was Overall Response Rate (ORR) via RECIST. Secondary endpoints included progression-free survival (PFS) and safety. Results: Of 132 patients receiving neoadjuvant therapy, 25 transitioned to definitive CRT (median age 63.6 years; 42% HPV+). Within this cohort, 76% received combination ICI + chemotherapy as induction, while 24% received ICI monotherapy. The post-neoadjuvant ORR was 83.3% (CR: 16.7%; PR: 66.7%). Neoadjuvant therapy did not delay the initiation of definitive CRT in any patients. Safety was favorable; only two patients (8%) experienced Grade 3+ toxicities during the neoadjuvant phase. At a median follow-up of 7.8 months, the 6-month PFS was 91.0%. Notably, a Combined Positive Score (CPS) >=1 was associated with significantly deeper radiological responses compared to CPS < 1 (p < 0.05). Conclusions: Neoadjuvant ICI and chemotherapy followed by definitive CRT is a feasible and well-tolerated strategy for LA-HNSCC. These findings suggest that induction immunotherapy does not compromise the delivery of definitive local therapy and provides promising early oncologic outcomes, particularly in CPS-positive disease.