Multicenter randomized phase 2 trial of nivolumab-ipilimumab versus docetaxel in R/M HNSCC progressing on nivolumab

Treatment options after PD-1 inhibition for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) are limited. The multicenter randomized phase 2 OPTIM trial in Germany compared nivolumab-ipilimumab (NIVO-IPI) versus docetaxel (DOCE) in adults with R/M HNSCC after progression on nivolumab. The 14 patients in the NIVO-IPI arm receivde nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks, whereas the 16 patients in the DOCE arm received docetaxel 75 mg/m² every 3 weeks. Treatment was continued until progression or intolerance. The primary endpoint was objective response rate (ORR). The ORR was 0% in the NIVO-IPI arm and 17.6% in the DOCE-arm, whereas the median progression-free survival was 1.97 versus 3.66 months (p=0.036) and the median overall survival was 3.97 versus 11.9 months (p=0.356), respectively. Twelve-months overall survival rates were 28.6% and 44.6%. Outcomes were similar regardless of PD-L1 status. Treatment-emergent adverse events occurred in 84.6% of the NIVO-IPI patients and 81.3% of the DOCE patients, with grade ≥ 3 events in 38.5% and 68.8%, respectively. The authors conclude that docetaxel was associated with numerically superior survival at the cost of greater toxicity (graphical abstract).