Breakthrough in Head and Neck Cancer Treatment: FDA Approves Pembrolizumab for Perioperative Therapy
The US FDA has approved pembrolizumab as a new standard of care for perioperative treatment for patients with locally advanced head and neck cancer that expresses PD-L1, a first for this group of cancers and the biggest advance in two decades. The change is based on results from the KEYNOTE-689 trial, which showed significantly longer disease-free survival.
Pembrolizumab , an immune checkpoint inhibitor previously used to treat conditions such as melanoma and lung cancer, has just been approved by the FDA for use in the perioperative treatment of locally advanced resectable head and neck squamous cell carcinoma . The condition is the presence of PD-L1 expression (CPS ≥1), confirmed by an approved diagnostic test.
This is the first time a checkpoint inhibitor has been approved for pre- and post-surgery treatment in this group of cancers.
The new approval is based on results from the randomized, phase 3 KEYNOTE-689 clinical trial , conducted at Dana-Farber Brigham Cancer Center and Washington University School of Medicine, among others. The trial included 714 patients with stage 3 or 4A head and neck cancer. One group received pembrolizumab before, during, and after surgery, and the other group received only standard care.
The result? Median event-free survival was 51.8 months in the pembrolizumab group compared with 30.4 months in the control group – after a median follow-up of 38.3 months.
“This is the first approval of a checkpoint inhibitor for perioperative treatment and is a huge paradigm shift,” said Robert Haddad, MD , chair of Head and Neck Oncology at Dana-Farber and one of the principal investigators.
In addition to improved survival, patients receiving pembrolizumab had higher rates of major pathological response —meaning robust, immunologically induced tumor destruction detected at postoperative analysis. Importantly, immunotherapy did not delay surgery and was well tolerated—no new adverse events were reported.
“These findings represent a truly exciting time for our patients as this is the first advance in this field in more than two decades,” said Dr. Ravindra Uppaluri , a cancer surgeon at Dana-Farber and lead author of the study.
The new treatment regimen could benefit patients with head and neck cancer whose tumors express PD-L1 . PD-L1 is a protein that allows cancer cells to evade the immune response. Pembrolizumab blocks this mechanism, “uncovering” the tumor from the immune system.
The FDA approved the therapy based on a combined positive score (CPS) ≥1 , meaning that even moderate PD-L1 expression may qualify a patient for treatment.
Until now, the treatment of head and neck squamous cell carcinoma has been based mainly on surgery, radiotherapy and chemotherapy. Now, immunotherapy is entering clinical practice already at the perioperative stage , which can change the prognosis of many patients.
Results from the KEYNOTE-689 trial were also presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting , underscoring its importance in the oncology community.
The new therapy means not only more months of life without relapse , but also new hope for patients and oncologists who have so far had limited options for action in this difficult cancer location.
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