Neoadjuvant cemiplimab with platinum-doublet chemotherapy and cetuximab in locoregionally advanced head & neck squamous cell carcinoma (HNSCC): Updated pathologic response and survival.

e18117 Background: Locoregionally advanced HNSCC treated with surgery and adjuvant radiation (RT)-based treatment is associated with significant morbidity and modest survival rates. This pilot study evaluated the combination of neoadjuvant cemiplimab, platinum-doublet chemotherapy, and cetuximab. We report pathologic response and down-staging to justify omission of adjuvant RT, along with event-free survival (EFS) and overall survival (OS). Methods: 30 patients with resectable HNSCC warranting adjuvant RT were enrolled. Neoadjuvant treatment entailed a cetuximab loading dose and cemiplimab followed by three 21-day cycles of cisplatin/carboplatin, docetaxel, cetuximab, and cemiplimab prior to surgery. Adjuvant therapy recommendations were based on pathologic staging. ypT0-2N0 tumors without adverse features or ypT0-1N1 tumors with a major pathologic response (MPR) (<10% viable tumor) were offered adjuvant cemiplimab in place of RT. The primary endpoint was pathologic response rate and secondary endpoints were EFS and OS. Results: 30 patients (26 oral cavity) completed treatment; 1 declined surgery (29 evaluable). Clinical T3 / T4 tumors (AJCC 8th Ed) were present in 17 (59%)/ 9 (31%) patients. 19/29 (66%) had a MPR and 9/29 (31%) had a pathologic complete response (pCR). Of the 18 (62%) patients eligible for omission of adjuvant RT, 14 did not undergo RT and 12 received adjuvant cemiplimab. With a median follow-up of 12.3 months (range: 5.8-43.6), 26/29 (90%) remain event-free. The 3 events include 2 local recurrences (1 pCR and 1 non-MPR, both salvaged with no evidence of disease) and 1 unrelated death. 1-year EFS / OS is 92.7% (95% CI, 92.0-93.4%) / 96.9% (95% CI, 96.4 – 97.3%) and 98.3% (95% CI, 89.9-100) / 100% for all patients and patients with adjuvant RT omitted, respectively, per Kaplan-Meier analysis. 3/30 (10%) patients experienced a G3/4 AE attributed to the addition of cemiplimab; G3 transaminitis (1), G3 infusion related reaction (1); G3 myasthenia gravis + G4 myocarditis (resolved) outside the DLT window (1). Conclusions: Neoadjuvant cemiplimab with platinum-doublet chemotherapy and cetuximab has led to notable pathologic down-staging allowing for omission of adj RT with impressive early event-free and overall survival. Clinical trial information: NCT04722523 . EFS and OS. Patients included Efficacy Follow-up Number Median follow-up in months (range) EFS (%, 95% CI) OS (%, 95% CI) All 1-year 29 12.3 (5.8-43.6) 92.7 (92.0-93.4) 96.9 (96.4-97.3) Adjuvant RT omitted 1-year 14 14.0 (7.9-37.7) 98.3 (89.9-100) 100 cT3 1-year 17 12.9 (5.9-39.6) 98.6 (93.9-100) 100 cT4 1-year 9 11.3 (7.5-43.6) 83.0 (77.2-88.8) 90.5 (87.6-93.2) First 10 2-years 10 37.1 (17.0-43.6) 97.4 (94.3-100) 100