Neoadjuvant tislelizumab plus chemotherapy followed by salvage surgery and adjuvant tislelizumab for recurrent head and neck squamous cell carcinoma after radiotherapy: A single-arm, phase II trial.

6070 Background: Locoregional recurrence remains a significant challenge in head and neck squamous cell carcinoma (HNSCC) after surgery and radiotherapy. Salvage surgery is the best option if negative margins can be achieved, and this can be strengthened in the era of immunotherapy. However, some relevant questions remain unanswered. The objectives of this prospective study were to evaluate the efficacy and safety of neoadjuvant tislelizumab plus chemotherapy followed by salvage surgery and adjuvant tislelizumab for recurrent HNSCC after radiotherapy. Methods: In this phase II, single-arm study, eligible pts 18 years of age or older with locoregional recurrent HNSCC after radiotherapy received neoadjuvant therapy with tislelizumab (200 mg), albumin-bound paclitaxel (260 mg/m 2 ), and cisplatin (60-75 mg/m 2 ) Q3W for 2 cycles, followed by salvage surgery and adjuvant tislelizumab (200 mg) Q3W for 6 cycles. The primary endpoint was major pathologic response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS) and safety. Results: Between March 2022 and September 2023, 34 pts were enrolled. Median age was 56 (30-75) yrs, 20.6% smoking history, 20.6% alcohol history and 61.8% male. All pts completed neoadjuvant therapy with an ORR of 35.3% (12/34) and DCR of 94.1% (32/34). Twenty-six pts (23 OSCC, 3 OPSCC) successfully underwent surgery with MPR rate 19.2% (5/26), of which the pCR rate was 15.4% (4/26). At median follow-up of 15.1 months, 1-year EFS was 63.4% and 1-year OS was 82.5% for per-protocol population. Twenty-five pts complained symptoms included pain, trismus, dysphagic, and speech disorders at baseline visit, and 84% (21/25) achieved remission after 2 cycles of neoadjuvant therapy. Grade 1-2 adverse events (AEs) with an incidence greater than 10% include 94.1% alopecia, 38.2% fatigue, 35.3% anorexia, 17.6% hypothyroidism and 14.7% anemia. Grade 3-4 adverse events (AEs) occurred in 1 pts (2.9%) with G3 hyperglycemia. Conclusions: Neoadjuvant and adjuvant tislelizumab with salvage surgery is well tolerated. The 1-year EFS and OS compared favorably with historical data. These encouraging results warrant further investigations. Clinical trial information: ChiCTR2100054296.