Breakthrough Immunotherapy Helps Patients With Locally Advanced Head and Neck Cancer
A pivotal advance in the treatment of locally advanced head and neck cancer centers on pembrolizumab, an immunotherapy drug already used in several cancers. In a recent trial, this therapy was integrated into a comprehensive treatment plan that combines surgery, radiotherapy, and chemotherapy, and it showed a remarkable improvement in how long patients live without the disease progressing.
The Challenge of Locally Advanced Disease
Many patients with head and neck cancers are diagnosed at a stage where the tumor is large and involves nearby structures, yet without distant metastasis. In the Brazilian clinical landscape, about eight in ten cases are identified at this locally advanced stage, underscoring the need for more effective strategies. Traditional approaches prioritize surgical removal, but the anatomy around the throat, tongue, and surrounding mucosa is complex. Even skilled surgeons may face trade-offs between complete tumor removal and preserving critical functions, including breathing and swallowing. This is why combining surgery with radiotherapy and chemotherapy has been the standard route for many years.
How Pembrolizumab Works
Pembrolizumab targets the PD-1/PD-L1 pathway, a molecular mechanism tumors use to hide from the immune system. By blocking these interactions, pembrolizumab helps T-cells recognize and attack cancer cells that were masking themselves from immune surveillance. While not every tumor responds, head and neck cancers—particularly those with a robust immune presence—tend to be more sensitive to this approach when integrated into multimodal therapy.
The KEYNOTE-689 Trial: Design and Outcomes
The KEYNOTE-689 trial enrolled 714 patients with locally advanced, resectable head and neck squamous cell carcinoma. Participants were randomized to receive pembrolizumab in addition to standard therapy before and after surgery, along with radiotherapy and, when appropriate, chemotherapy. The goal was to determine how long patients stayed free from disease progression and how overall outcomes compared with the standard approach alone.
In the group that received pembrolizumab, patients demonstrated a substantial extension in progression-free survival. On average, disease remained controlled for about 52 months, compared with roughly 30 months in those treated with the conventional approach. Among patients whose tumors expressed higher levels of PD-L1, the benefit was even more striking: nearly 60 months of disease control with pembrolizumab versus about 26 months with standard therapy. These results suggest that the drug can meaningfully extend the window of time patients live without cancer returning in the head and neck region.
What This Means for Patients and Clinicians
The findings from KEYNOTE-689 represent a potential shift in the standard of care for locally advanced head and neck cancer. By combining pembrolizumab with surgery, radiotherapy, and chemotherapy, clinicians may offer patients a longer, higher-quality period of disease control and, in many cases, improved long-term survival. As with any cancer therapy, individual results vary, and access, cost, and eligibility criteria will influence how broadly this approach is adopted in different health systems.
Safety Considerations and Management
As with other immunotherapies, pembrolizumab can trigger immune-related side effects, including thyroid, intestinal, and lung inflammation. Most adverse events are manageable and reversible with appropriate medical care, and the overall safety profile observed in trials has supported its use in combination regimens. Ongoing monitoring during the full year of treatment is essential to promptly address any immune-related complications.
Prevention and Risk Factors
While advances in therapy offer hope, prevention remains foundational. The most important risk factors for head and neck cancers continue to be tobacco and alcohol use, with HPV infections emerging as a growing concern in recent years. Public health efforts to reduce these risks are crucial to lowering the incidence of locally advanced disease in the long term.
Looking Ahead
As immunotherapy becomes more integrated with surgery and radiotherapy, patients with locally advanced head and neck cancer may experience meaningful improvements in both survival and quality of life. The success of KEYNOTE-689 underscores the importance of multidisciplinary care and the potential for immunotherapies to alter the trajectory of a disease that has historically posed significant treatment challenges.
