New hope for locally advanced head and neck cancer: pembrolizumab
Locally advanced tumors in the head and neck region pose a formidable challenge. They are often confined to the mucosal areas, yet their proximity to the airway, esophagus, and vital vessels makes surgical removal delicate and potentially mutilating. Radiotherapy and chemotherapy add to the cure efforts but can take a heavy toll. A recent development offers a new strategy: pembrolizumab, an immunotherapy from MSD, used in combination with standard treatment around the time of surgery to boost the body’s own defenses against cancer.
What is pembrolizumab and how does it work?
Pembrolizumab, commonly referred to by clinicians as pembro, blocksPD-1, a checkpoint on immune cells. Some cancers exploit PD-1/PD-L1 to escape immune detection by acting like a mask. By inhibiting this interaction, pembrolizumab helps T cells recognize and attack tumor cells more effectively. While not every tumor responds, head and neck cancers—especially those with a robust inflammatory environment—often show meaningful benefits from this approach.
The KEYNOTE-689 trial: design and results
The KEYNOTE-689 study enrolled 714 patients with locally advanced head and neck cancer. They were randomized to receive the immunotherapy pembrolizumab plus standard care (which could include surgery, radiotherapy, and chemotherapy) or standard care alone. The regimen begins before surgery with two pembrolizumab infusions three weeks apart, continues after surgery with three more infusions, and is followed by radiotherapy, with additional chemotherapy as needed. After the end of radiotherapy/chemotherapy, roughly 12 more pembrolizumab cycles complete a year-long treatment plan.
Results showed a clear advantage for those treated with pembrolizumab. The median time before disease progression or recurrence was about 52 months in the immunotherapy group, compared with about 30 months in the standard-treatment group. Among patients whose tumors expressed higher levels of PD-L1, the benefit was even more striking: roughly 60 months versus 26 months.
Safety and practical considerations
Immunotherapies can cause immune-related side effects as the body’s defenses may become overactive. In the KEYNOTE-689 population, some patients experienced thyroiditis, colitis, or pneumonitis. Most adverse events are manageable and reversible with appropriate medical care. The overall safety profile supports its use in a carefully monitored, multidisciplinary treatment plan that spans roughly a year and integrates surgery, radiotherapy, chemotherapy, and immunotherapy.
Why this matters for patients and clinicians
For surgeons and oncologists, the trial provides a compelling argument to incorporate pembrolizumab into the perioperative and adjuvant setting for locally advanced head and neck cancer. The combination strategy can enhance tumor control and extend disease-free intervals, translating into longer periods of life with a better quality of life. While these results are encouraging, clinicians will tailor therapy to each patient’s biology, health status, and preferences, and access to pembrolizumab remains a key consideration in many health systems.
Prevention still matters
Even as treatments advance, prevention remains essential. The major risk factors for head and neck cancers—tobacco use and alcohol consumption—continue to drive incidence. HPV infection is another important contributor, and vaccination and screening efforts play an increasing role in reducing the burden of this disease. Public health measures to curb risk factors are as important as advances in therapy.
Conclusion
The KEYNOTE-689 trial represents a turning point in the management of locally advanced head and neck cancer. Pembrolizumab, used in combination with standard care around the time of surgery, has the potential to double progression-free survival for many patients and, in those with high PD-L1 expression, provide even greater benefit. As the medical community integrates these findings into practice, ongoing evaluation of long-term outcomes, accessibility, and cost will be essential to ensure widespread, equitable impact.
