Tislelizumab plus nab-paclitaxel and cisplatin as induction immunochemotherapy for organ preservation of locally advanced hypopharyngeal squamous cell carcinoma: a single-arm phase II trial

Introduction
Hypopharyngeal squamous cell carcinoma (HPSCC) has the poorest prognosis among head and neck cancer subtypes. The efficacy, role in organ preservation, safety, and biomarkers of induction immunochemotherapy for HPSCC require further investigation.
Methods
This phase II trial enrolled untreated patients with locally advanced (T1N + M0, T2-4N0-3M0) HPSCC. Induction therapy consisted of tislelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (75 mg/m2) i.v. on day 1 of each 3-week cycle for two cycles (ChiCTR2200060094). The primary endpoint was the larynx preservation rate (LPR) at 3 months. Secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, disease control rate (DCR), larynx preservation survival (LPS), progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), and safety. Sample size was calculated using Simon’s optimal two-stage design, with an expected LPR of 65% for chemotherapy and 85% for immunochemotherapy. Survival analysis was carried out using the Kaplan–Meier method.
Results
Between 25 May 2022, and 15 November 2023, 45 patients were enrolled and all completed two cycles of induction immunochemotherapy. At the data cut-off on 15 March 2024, the 3-month LPR was 86.7% [39/45, 95% confidence interval (CI) 0.73% to 0.95%]. The ORR and DCR were 62.2% (28/45) and 100% (45/45), respectively. Twenty-eight patients underwent surgery. The pCR rate was 21.4% (6/28). With a median follow-up of 11.6 months (95% CI 10.1-17.7 months), the median LPS, PFS, DFS, and OS were not reached. The 12-month LPS, PFS, DFS, and OS rates were 66.7% (95% CI 52.2% to 85.2%), 69.8% (95% CI 56.0% to 87.1%), 81.6% (95% CI 66.6% to 99.9%), and 77.4% (95% CI 63.4% to 94.3%), respectively. All patients experienced treatment-related adverse events (TRAEs). The incidence of ≥ grade 3 TRAEs was 31% (14/45), with neutropenia being the most common (18%, 8/45). Common immune-related adverse events included grade 1-2 thyroid dysfunction and rash. No ≥ grade 3 immune-related adverse events occurred. No TRAEs led to treatment discontinuation.
Conclusions
Tislelizumab plus nab-paclitaxel and cisplatin appears to be a promising induction immunochemotherapy regimen for organ preservation, showing encouraging efficacy and a favorable safety profile in untreated locally advanced HPSCC, warranting further investigation.