Neoadjuvant sintilimab and chemotherapy followed by transoral surgery for HPV-positive resectable oropharyngeal cancer: a single-arm, two-centre, phase 2 trial.

Abstract

Background: Treatment deintensification, such as neoadjuvant immunochemotherapy and transoral surgery, has shown promise but remains under investigation in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV⁺OPSCC). We aimed to explore the efficacy and safety of neoadjuvant immunochemotherapy and the feasibility of sequential transoral surgery in patients with resectable HPV⁺OPSCC.

Methods: In this single-arm, two-centre, phase 2 trial, patients with resectable HPV⁺OPSCC (clinical stage T2-4N0-3M0) were recruited and received two cycles of neoadjuvant sintilimab, cisplatin, and nab-paclitaxel every three weeks, followed by transoral surgery, including transoral robotic surgery (TORS). The primary endpoint was major pathological response (MPR), defined as the residual viable tumor of less than or equal to 10% in the primary lesion. The study is registered with Chinese Clinical Trial Registry (ChiCTR2200058650) and is ongoing.

Findings: Between April 13, 2022 and November 17, 2023, 27 patients were enrolled and all received two cycles of neoadjuvant immunochemotherapy, which all achieved partial responses. Among them, 25 patients received radical surgery (21 TORSs and 4 transoral surgeries). MPR was achieved in 24 patients (24/25, 96.0%), including 17 (17/25, 68.0%) with pathological complete response (pCR). Grade 1-2 treatment-related adverse events (TRAE) occurred in 24 of 27 patients (88.9%), including skin rash (12/27, 44.4%), alopecia (10/27, 37.0%), nausea (8/27, 29.6%), fatigue (8/27, 29.6%), and pain (8/27, 29.6%). Only one patient (1/27, 3.7%) experienced grade 3 TRAEs with no treatment-related death. For the per-protocol population, the 2-year DFS and OS were both 96.0% (95% CI: 88.6%-100.0%). Most patients experienced improved symptoms including pain and swallowing at 3 months post-surgery, and remained stable at 6 months and 1 year post-surgery. Circulating tumor HPV-DNA clearance had a trend to occur in patients with pCR.

Interpretation: Neoadjuvant immunochemotherapy and sequential transoral surgery, including TORS, appears to be a feasible strategy that yields favorable oncologic and functional outcomes for patients with resectable HPV⁺OPSCC.

Funding: Innovent Biologics.