Neoadjuvant sintilimab and platinum-doublet chemotherapy followed by transoral robotic surgery for HPV-associated resectable oropharyngeal cancer: Single-arm, phase II trial.

6011 Background: De-escalation treatments for HPV-associated (HPV+) oropharyngeal cancer (OPC) have been well discussed. Meanwhile, the combination of anti-PD-1 therapy and chemotherapy (immunochemotherapy, ICT) and transoral robotic surgery (TORS) shows promising results in OPC, especially in HPV+ ones. This study aims to investigate the efficacy and safety of neoadjuvant ICT and sequential TORS to reduce functional impairments and omit adjuvant radiotherapy for resectable HPV+ OPC. Methods: In the single-arm, phase II trial, patients with resectable HPV+OPC (cT2-4N0-3M0, AJCC 8.0) were recruited and received neoadjuvant sintilimab (200mg), platinum (cisplatin 60mg/m 2 , or carboplatin AUC=5), and paclitaxel (nab-paclitaxel 260mg/m 2 , or docetaxel 75mg/m 2 ) every 3 weeks for 2 cycles, followed by radical surgery (with TORS as an option). The primary endpoint was major pathological response (MPR; defined as residual viable tumor of less than or equal to 10%) in the primary lesion. The secondary endpoints include pathologically complete response (pCR) of all resected lesions, objective response rate (ORR) according to RECIST 1.1, disease-free survival (DFS) rate and overall survival (OS) rate at 1 and 3 years, quality of life (QoL) by EORTC QLQ-H&N35 questionnaire. Results: From February 1, 2022 to November 30, 2023, 27 patients were enrolled and received 2 cycles of neoadjuvant ICT. After neoadjuvant therapy, all 27 cases achieved partial response (PR), the ORR was 100%. Among them, 25 patients received radical surgery (per-protocol population), including 21 with TORSs. The pathological evaluation showed 24 patients (96.0%) achieved MPR, and 13 (52.0%) achieved pCR of all samples including primary lesions and resected lymph nodes. Grade 1-2 treatment-related adverse events (TRAE) occurred in 24/27 patients (88.9%). The most common TRAEs included rash (12, 44.4%), alopecia (10, 37.0%), nausea (8, 29.6%) and weakness (8, 29.6%), while only one patient (3.7%) experienced grade 3 TRAEs, including febrile leukopenia, pneumonia and diarrhea. These adverse reactions were manageable and no surgical delay occurred. After the surgery, the majority of patients had active follow-up without any adjuvant treatment (19/25, 76%), while 4 patients received adjuvant anti-PD-1 therapy and only 2 had adjuvant radiotherapy. At an average follow-up time of 8.2 months, the 6-month DFS and OS were both 100%. Furthermore, compared to the baseline, 22 patients (88%) reported similar or improved QoL scores at 3 months after surgeries. Conclusions: Neoadjuvant sintilimab plus platinum-doublet chemotherapy and sequential TORS achieved satisfactory pathological response, favorable functional preservation and tolerable toxicity in patients with resectable HPV+OPC. Further follow-up is warrant to confirm long-term survival benefits. Clinical trial information: ChiCTR2200058650.