Neoadjuvant Immunotherapy for Head and Neck Squamous Cell Carcinoma: Treatment Response, Complications, and De-escalation

Introduction: Following landmark trials, neoadjuvant immunotherapy (neo-IO) is increasingly being used for head and neck mucosal (mSCC) and skin (cSCC) squamous cell cancers. A paucity of real-world data exists to evaluate outcomes under this new paradigm, including response rates, adverse events (AEs), and potential for de-escalation of subsequent surgery or radiation.

Methods: We conducted a retrospective chart review of patients who received pre-operative IO for cT1-4 cSCC or mSCC at a single tertiary institution (January 2022-present). Regimens included cemiplimab (29%), pembrolizumab/carboplatin/paclitaxel (19%), nivolumab (19%), 5-azacytidine/nivolumab (13%), or IO102-IO103 vaccine/pembrolizumab (13%). Treatment response, AEs, perioperative complications, and changes to surgical and radiation planning were recorded.

Results: The cohort (n=52) included 20 (38%) cSCC and 32 (62%) mSCC (61% HPV+). 31% of mSCC had cT3-4 disease, 25% were cN2-3. 35% of cSCC were cT3-4, 15% cN2-3, and 50% had locoregionally recurrent disease. Pre-operative objective response rate (ORR) to neo-IO was 95% for cSCC and 44% for mSCC; notably, 7 patients (6 cSCC, 1 mSCC) achieved complete response (CR) and did not require surgery. 10 patients (19%) (9 cSCC, 1 mSCC) had pathologic complete response (pCR), and 3 (6%) (1 cSCC, 2 mSCC) had major pathologic response (≤10% residual tumor). At the time of analysis, 80% cSCC and 84% mSCC were disease-free. 12 (29%) patients experienced grade ≥3 pre-operative AEs: pulmonary embolism (3), immune-related hepatitis (2), and adrenal insufficiency (2). Of the 42 surgical patients, 14 (33%) experienced perioperative complications: hemorrhage/hematoma (4), wound dehiscence (2), and flap failure (2). Analysis of changes to surgical and radiation therapy planning are underway.

Conclusions: Neo-IO demonstrated substantial clinical and pathologic responses in patients with head and neck SCC, with a subset achieving CR without surgery. These preliminary data support future investigation into treatment de-escalation and multivariable analyses by regimen and tumor subtype.