The phase 3 clinical trial KEYNOTE-689 shows that incorporating the monoclonal antibody pembrolizumab before and after surgery, alongside standard of care, improves event-free survival in patients with locally advanced head and neck squamous cell carcinoma.
Dr Irene Braña, a medical oncologist and head of the Head and Neck Cancer Group at VHIO, participated in this trial. The results have been presented at the annual AACR meeting (25–27 April) in Chicago
Researchers from the VHIO Head and Neck Cancer Group, led by Dr Irene Braña, in collaboration with the VHIO Radiotherapy Oncology Group and the Maxillofacial Surgery and Pathology teams at Vall d’Hebron University Hospital, contributed to the international KEYNOTE-689 clinical trial.
The study results are being presented today at the American Association for Cancer Research (AACR) Annual Meeting—taking place in Chicago from 25 to 27 April.
Limited advances in treatment in recent decades
Locally advanced head and neck squamous cell carcinoma is a severe disease with limited advances in treatment options in recent decades. Standard of care for these patients typically includes post-surgery radiotherapy, or radiotherapy combined with chemotherapy for patients with a worse prognosis. Unfortunately, about one-third of patients relapse, and only half survive for five years.
“On one hand, we know that pembrolizumab, a monoclonal antibody targeting the PD-1 protein, is a critical part of first-line treatment for recurrent and metastatic head and neck squamous cell carcinoma,” explains Dr Irene Braña, medical oncologist at Vall d’Hebron University Hospital, head of the VHIO Head and Neck Cancer Group, and co-author of the study. “On the other hand, clinical trials have shown that adding this drug to established neoadjuvant and adjuvant regimens (before and after surgery) improves clinical outcomes in patients with various types of tumours. Furthermore, two phase 2 trials in head and neck cancer suggest that adding perioperative pembrolizumab leads to lower relapse rates and better disease-free survival.”
Adding immunotherapy to standard of care before and after surgery
The phase 3 KEYNOTE-689 trial, presented today, evaluates the efficacy and safety of pembrolizumab before and after surgery, combined with standard of care (radiotherapy with or without chemotherapy), compared to standard of care alone, in patients with locally advanced head and neck tumours.
A total of 714 patients participated in the trial, 321 of whom received pembrolizumab before and after surgery, alongside standard of care with preoperative radiotherapy, with or without chemotherapy. Patients were also categorised based on their Combined Positive Score (CPS), which measures the expression of the PD-L1 biomarker on tumour and immune cells and is commonly used to select patients who may benefit from immunotherapy.
Event-free survival at 36 months was 57.6% in the pembrolizumab group versus 46.4% in the control group across all participants; 59.8% versus 45.9% in patients with CPS ≥10 (more responsive to immunotherapy); and 58.2% versus 44.9% in patients with CPS ≥1. The benefits were statistically significant in the three groups.
“The standard of care for patients with locally advanced head and neck squamous cell carcinoma has not substantially changed since 2004 when the addition of chemotherapy to postoperative radiotherapy became the established treatment for high-risk disease,” states Dr Braña.
“The results from the KEYNOTE-689 trial reveal that a new therapeutic strategy based on adding immunotherapy—in this case, an immune checkpoint inhibitor, before and after surgery—significantly improves event-free survival in these patients. This opens up new therapeutic opportunities to reduce their risk of relapse. The close collaboration between surgeons, medical oncologists, and radiation oncologists has been key in conducting this study. We are thrilled that our patients were among the first to benefit from this strategy, which we hope will become the standard of care in the future,” she concludes.
Reference
AACR 2025 session details
Session CTPL01 – Advances in Immunotherapy
27 April 2025, 8:00 p.m. CEST
Arie Crown Theater – McCormick Lakeside Center (Level 2)
CT001 – Neoadjuvant and adjuvant pembrolizumab plus standard of care (SOC) in resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC): Phase 3 KEYNOTE-689 study
Ravindra Uppaluri1, Robert I. Haddad1, Yungan Tao2, Christophe Le Tourneau3, Nancy Y. Lee4, William Westra5, Rebecca Chernock6, Makoto Tahara7, Kevin Harrington8, Arkadiy L. Klochikhin9, Irene Braña10, Gustavo Vasconcelos Alves11, Brett G.M. Hughes12, Marc Oliva13, Iane Pinto Figueiredo Lima14, Tsutomu Ueda15, Tomasz Rutkowski16, Ursula Schroeder17, Paul-Stefan Mauz18, Thorsten Fuereder19, Simon Laban20, Nobuhiko Oridate21, Aron Popovtzer22, Nicolas Mach23, Yevhen Korobko24, Diogo Alpuim Costa25, Anupama Hooda-Nehra26, Cristina P. Rodriguez27, R. Bryan Bell28, Cole Manschot29, Kimberly Benjamin29, Burak Gumuscu29, Douglas Adkins6
Chairs: Jayesh Desai. Peter MacCallum Cancer Centre, Melbourne, Australia & Antoni Ribas. UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA
