Randomized non-comparative phase II trial of nivolumab plus paclitaxel in subjects with recurrent/metastatic head and neck squamous cell carcinoma unable for cisplatin-based chemotherapy. NIVOTAX TTCC study

Background: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) who are ineligible for cisplatin have limited treatment options, and the role of chemoimmunotherapy in this population remains unexplored.Methods: NIVOTAX was a randomized, non-comparative, multicenter, phase II trial evaluating paclitaxel plus nivolumab (nivotax) in previously untreated, platinum-ineligible R/M HNSCC (platinum-refractory, unfit, or cumulative dose 225 mg/m).Patients were randomized 2:1 to weekly paclitaxel (80 mg/m) plus biweekly nivolumab (240 mg) or weekly cetuximab (250 mg/m) for 12 weeks, followed by maintenance nivolumab q4 weeks or weekly cetuximab for up to 24 months.The primary endpoint was 2-year overall survival (2yOS).Key secondary endpoints were median OS; progression-free survival (PFS), overall response rate (ORR) and safety.Results: 141 patients were randomized (nivotax, n=93; Erbitax, n=48).Baseline characteristics were balanced.After a median follow-up of 12.1 months (33.1 months for alive patients), 2yOS was 24.7% (95% CI 15.9-33.5)with nivotax and 13.4% (95% CI 3.6-23.2) with Erbitax.Median OS, PFS and ORR were similar in both arms.No differences were observed by age, PD-L1 CPS and Karnofsky Performance Scale.Grade >3 treatment-related adverse events (AEs) occurred in 38% and 43% of patients, respectively.Higher mortality was observed in the nivotax arm (18% vs 8.3%) due to higher occurrence of respiratory AEs deemed treatment unrelated by investigators.Conclusions: The primary endpoint of 2yOS was met.However, respiratory AEs and associated mortality emerged as a safety concern in the nivotax arm, limiting further evaluation of this regimen.