Top Line: Does perioperative immunotherapy improve outcomes for resectable head and neck cancer?
The Study: Immunotherapy continues to play a relatively limited role in the management of non-metastatic head and neck squamous cell carcinoma (HNSCC). KEYNOTE-689 was a randomized, phase III trial that sought to determine if the addition of perioperative pembrolizumab improved event free survival in patients planned to have surgery for HNSCC. It included 714 patients with p16+ T4N0-2 oropharyngeal cancer or stage III-IVA, p16- SCC of the oral cavity, oropharynx, larynx, or hypopharynx. N3 disease was not included. They were randomized to receive 2 cycles of neoadjuvant pembrolizumab prior to surgery or go straight to surgery. Standard of care adjuvant therapy consisted of radiation in ALL patients including RT alone for low risk patients and chemoradiation for high risk patients. Those in the pembro arm received adjuvant pembro along with either RT or CRT. As recently presented at AACR 2025, the addition of pembro significantly prolonged event free survival (51.8 v 30.4 months). The rate of major pathology response (<10% residual disease) after 2 cycles of neoadjuvant pembro was 9.3%. There was no difference in overall survival at this point. Since this was in abstract form, we’ll have to await full publication to see key breakdowns in patient and treatment characteristics. For example, what was the rate of positive margins or extranodal extension, and what proportion of patients received quad-modality therapy?
TBL: Abstract reporting of KEYNOTE-689 shows a significant improvement in event free survival when perioperative pembrolizumab is added to standard adjuvant therapy for resectable HNSCC. | Uppaluri, AACR 2025
The Study: Immunotherapy continues to play a relatively limited role in the management of non-metastatic head and neck squamous cell carcinoma (HNSCC). KEYNOTE-689 was a randomized, phase III trial that sought to determine if the addition of perioperative pembrolizumab improved event free survival in patients planned to have surgery for HNSCC. It included 714 patients with p16+ T4N0-2 oropharyngeal cancer or stage III-IVA, p16- SCC of the oral cavity, oropharynx, larynx, or hypopharynx. N3 disease was not included. They were randomized to receive 2 cycles of neoadjuvant pembrolizumab prior to surgery or go straight to surgery. Standard of care adjuvant therapy consisted of radiation in ALL patients including RT alone for low risk patients and chemoradiation for high risk patients. Those in the pembro arm received adjuvant pembro along with either RT or CRT. As recently presented at AACR 2025, the addition of pembro significantly prolonged event free survival (51.8 v 30.4 months). The rate of major pathology response (<10% residual disease) after 2 cycles of neoadjuvant pembro was 9.3%. There was no difference in overall survival at this point. Since this was in abstract form, we’ll have to await full publication to see key breakdowns in patient and treatment characteristics. For example, what was the rate of positive margins or extranodal extension, and what proportion of patients received quad-modality therapy?
TBL: Abstract reporting of KEYNOTE-689 shows a significant improvement in event free survival when perioperative pembrolizumab is added to standard adjuvant therapy for resectable HNSCC. | Uppaluri, AACR 2025