Tislelizumab as adjuvant therapy following endoscopic surgery for resectable recurrent nasopharyngeal carcinoma: A phase 2 randomized clinical trial.

Abstract

e18078 Background: In recent years, endoscopic surgery has become the first-line treatment for surgically resectable recurrent nasopharyngeal carcinoma (rNPC); however, the role of programmed death 1 (PD-1) blockade in patients after endoscopic surgery for rNPC remains unknown. This study aimed to evaluate the efficacy and safety of tislelizumab as adjuvant consolidation therapy. Methods: This was a single-center, open-label, randomized, controlled, phase 2 trial. Eligible patients aged 18–70 years were histopathologically diagnosed with undifferentiated or differentiated nonkeratinizing rNPC. Patients with rNPC were randomized to receive endoscopic surgery alone or endoscopic surgery followed by tislelizumab treatment. Tislelizumab was administered as a 200 mg intravenous infusion every 3 weeks until disease progression or unacceptable toxicity was confirmed. The primary endpoint was progression-free survival (PFS) at 1 year, and secondary endpoints included 1-year progression-free interval (PFI), 1-year overall survival (OS), and safety. Results: The trial is ongoing. Forty-two patients had been enrolled between November 23, 2021 and May 8, 2024. At a median follow-up of 18 months (IQR 10–27), the 1-year PFS was significantly higher in the tislelizumab group (94%, 95% confidence interval (CI) 83–100%) than in the endoscopic surgery alone group (57%, 95% CI 38–85%). The 1-year PFI was also higher in the tislelizumab group (100%, 95% CI: 100%–100%) than in the endoscopic surgery alone group (60%, 95% CI: 40%–89%). No significant difference in the 1-year OS was observed at the data cutoff. Common surgery-related adverse events in the endoscopic surgery group included skull base osteonecrosis (30%), with three cases of grade 2 and three cases of grade 3 or higher AEs. In the tislelizumab group, 18% of patients with osteonecrosis only experienced grade 1 AEs. Grade ≥3 immune-related adverse events (irAEs) occurred in 9% of tislelizumab recipients, and the most common irAEs in this group were hypothyroidism, affecting 27%, and pruritus, observed in 9%. Conclusions: Tislelizumab as adjuvant therapy significantly enhanced PFS and PFI, with a favorable safety profile. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with resectable rNPC following endoscopic surgery. Clinical trial information: NCT05092217 .