Top Line: Does adjuvant immunotherapy improve outcomes in patients with resected, high risk HNSCC?
The Study: Adjuvant chemoradiation has been the standard approach for high risk (extranodal extension or positive margins) HNSCC for many years now. Recently, KEYNOTE-689 reported improved event free survival when perioperative pembrolizumab was added to standard therapy for resectable HNSCC. In NIVOPOST-OP, 666 patients with high risk HNSCC were randomized to receive adjuvant radiation (66 Gy in 33 fractions) and q3 weeks cisplatin with or without nivolumab. The most common primary site was the oral cavity (58%). High risk features included ENE (63%), positive margins (1mm or less, 58%), multiple perineural invasion (56%), or 4 or more nodes without ENE (13%). Few (5%) had p16+ tumors. In the nivo arm, nivo was started roughly 2 weeks post-op and prior to starting CRT. It was continued along with each cisplatin dose, and then it was given once every 4 weeks for up to 6 months after CRT. The primary endpoint of DFS was significantly improved with the addition of nivolumab (HR 0.76, p=.034). At 3 years, the rate of DFS was 63.1% with nivo versus 52.5% without. This was driven by a significant decrease in locoregional relapse with no significant difference in distant relapse. However, grade 4 adverse events were higher with nivo (10% v 5%).
TBL: Adding nivolumab to adjuvant chemoradiation for resected, high risk HNSCC reduced locoregional recurrence and significantly increased DFS while modestly increasing high grade adverse events. | Bourhis, Lancet 2025
The Study: Adjuvant chemoradiation has been the standard approach for high risk (extranodal extension or positive margins) HNSCC for many years now. Recently, KEYNOTE-689 reported improved event free survival when perioperative pembrolizumab was added to standard therapy for resectable HNSCC. In NIVOPOST-OP, 666 patients with high risk HNSCC were randomized to receive adjuvant radiation (66 Gy in 33 fractions) and q3 weeks cisplatin with or without nivolumab. The most common primary site was the oral cavity (58%). High risk features included ENE (63%), positive margins (1mm or less, 58%), multiple perineural invasion (56%), or 4 or more nodes without ENE (13%). Few (5%) had p16+ tumors. In the nivo arm, nivo was started roughly 2 weeks post-op and prior to starting CRT. It was continued along with each cisplatin dose, and then it was given once every 4 weeks for up to 6 months after CRT. The primary endpoint of DFS was significantly improved with the addition of nivolumab (HR 0.76, p=.034). At 3 years, the rate of DFS was 63.1% with nivo versus 52.5% without. This was driven by a significant decrease in locoregional relapse with no significant difference in distant relapse. However, grade 4 adverse events were higher with nivo (10% v 5%).
TBL: Adding nivolumab to adjuvant chemoradiation for resected, high risk HNSCC reduced locoregional recurrence and significantly increased DFS while modestly increasing high grade adverse events. | Bourhis, Lancet 2025