MedNet.nl: The addition of perioperative pembrolizumab to standard treatment for resectable locally advanced squamous cell carcinoma of the head and neck (HNSCC) leads to a significant improvement in event-free survival (EFS). The effect was independent of PD-L1 expression in the phase 3 KEYNOTE-689 trial, researchers reported at the ASCO Congress.
KEYNOTE-689 included patients with squamous cell carcinoma of the larynx/hypopharynx/mouth cavity (stage III/IVa) or oropharynx (stage III/IVa p16− or stage III T4 N0−2 p16+). They were randomized 1:1 to standard care (surgery plus postoperative radiotherapy, with or without concomitant cisplatin), or to this treatment plus perioperative pembrolizumab (2 cycles neoadjuvant, 3 cycles concurrent with (chemo)radiotherapy, and 12 cycles adjuvant). The primary endpoint was EFS.
After a median follow-up of 38.3 months, the EFS differed significantly between the two study arms. In the pembrolizumab arm, the median EFS was 51.8 months, compared with 30.4 months in the standard care arm (HR=0.73). After 36 months, 57.6% and 46.4% were event-free in the 2 groups, respectively. Both the groups with high and low PD-L1 expression benefited from perioperative pembrolizumab; for a combined positive score of at least 10 or at least 1, the HRs were 0.66 and 0.70, respectively. Also, major pathologic responses occurred more frequently when immunotherapy was added; at 9.4% versus 0.0%. Pathologic complete responses occurred in 3.0% versus 0.0%. Metastasis-free survival was also better, at 51.8 months versus 35.7 months (HR=0.71). Metastasis-free survival at 36 months was 68.4% versus 61.1%.
Addition of pembrolizumab resulted in only a modest increase in adverse events, although the treatment duration was significantly longer (9.1 vs 2.9 months). Grade 3 or worse adverse events occurred in 44.6% and 42.9%, respectively.
The investigators state that adding perioperative pembrolizumab will become a new standard treatment in this setting. This adds two potential new treatment options within a short time, as the NIVOPOSTOP study presented at this ASCO also had a positive result.
Bourhis J, Auperin A, Borel, et al. NIVOPOSTOP (GORTEC 2018-01): a phase III randomized trial of adjuvant nivolumab added to radio-chemotherapy in patients with resected head and neck squamous cell carcinoma at high risk of relapse. ASCO 2025, abstract LBA2.
This article was originally published in Dutch on MedNet.nl