Neoadjuvant and adjuvant pembrolizumab in head and neck cancer

Results from the KEYNOTE-689 trial, recently published on The New England Journal of Medicine, show that adding neoadjuvant and adjuvant pembrolizumab to standard care significantly improves event-free survival in patients with advanced head and neck cancer.

KEYNOTE-689 trial randomly assigned 714 patients with locally advanced head and neck squamous cell carcinoma to receive 2 cycles of neoadjuvant pembrolizumab and 15 cycles of adjuvant pembrolizumab (both at a dose of 200 mg every 3 weeks) in addition to standard care (pembrolizumab group) or standard care alone (control group), consisting in surgery and adjuvant radiotherapy with or without cisplatin. After a median follow-up of 38.3 months, 88% of all patients underwent surgery and neoadjuvant pembrolizumab did not affect the likelihood of surgical completion. 3-year event-free survival was 59.8% in the pembrolizumab group and 45.9% in the control group in patients whose tumors expressed PD-L1 with a combined positive score of 10 or more; in the total population, 3-year event-free survival was 57.6% in the pembrolizumab group and 46.4% in control group. No new safety signals were detected and potentially immune-mediated adverse events of grade 3 or higher occurred in 10% of the participants in the pembrolizumab group. As authors state, «Standard care for resectable locally advanced head and neck squamous cell carcinoma has remained relatively constant since 2004, when two pivotal randomized trials first established the addition of cisplatin to postoperative radiotherapy as the recommended treatment regimen for high-risk disease. The KEYNOTE-689 trial showed that the addition of neoadjuvant and adjuvant pembrolizumab to standard care conferred a significant improvement in event-free survival among patients with resectable locally advanced head and neck squamous cell carcinoma».