FDA approves pembrolizumab for resectable head and neck cancer with PD-L1 expression

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with resectable locally advanced head and neck squamous cell carcinoma whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.

The FDA approval is based on data from the pivotal KEYNOTE-689 study, a randomized, open-label phase 3 clinical trial in which patients who received pembrolizumab before, during and after standard-of-care surgery had longer event-free survival without the cancer coming back and higher rates of substantial tumor shrinkage prior to surgery. The study was led by investigators from Dana-Farber Brigham Cancer Center and Washington University School of Medicine in St. Louis.

This new regimen represents a substantial change in workflow for head and neck cancer care, offering appropriate patients the option of receiving pembrolizumab before surgery for resectable locally advanced head and neck cancer.

“These findings represent a truly exciting time for our patients, as it is the first advance in this field in over two decades,” said Dr. Ravindra Uppaluri, the study’s overall principal investigator, director of Head and Neck Surgical Oncology at Dana-Farber and Brigham and Women’s Hospital, and Brigham and Women’s Hospital Endowed Chair in Otolaryngology.

“This is the first approval of a checkpoint inhibitor in the curative, perioperative setting and it represents a massive paradigm shift in how we manage surgically treated head and neck cancer going forward,” said Dr. Robert Haddad, chief of the Division of Head and Neck Oncology and the McGraw Chair in Head and Neck Oncology at Dana-Farber, professor of medicine at Harvard Medical School and the Dana-Farber Brigham Cancer Center principal investigator and member of the KEYNOTE-689 steering committee.

The KEYNOTE-689 trial randomized 714 patients with newly diagnosed stage 3 or stage 4A head and neck squamous cell cancer to receive either pembrolizumab before (called neoadjuvant), during and after (called adjuvant) standard of care or standard of care alone. The investigators also measured the presence of the target of pembrolizumab, PD-L1, in tumors to determine if higher scores of PD-L1 in tumors would affect response to treatment.

The study met its primary endpoint showing that patients who received pembrolizumab had longer event-free survival. Median event-free survival was 51.8 months with pembrolizumab and 30.4 without after a median of 38.3 months of follow-up. The team also observed significantly higher rates of major pathologic response, a substantial immune mediated tumor destruction seen in surgical resections.

The treatment was found to be safe with no new observed side effects. Further, patients taking pembrolizumab received surgery in a timely manner and were not delayed by immunotherapy-related side effects prior to surgery.

The data was previously presented at the 2025 American Association of Cancer Research (AACR) Annual Meeting.

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with resectable locally advanced head and neck squamous cell carcinoma whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.

The FDA approval is based on data from the pivotal KEYNOTE-689 study, a randomized, open-label phase 3 clinical trial in which patients who received pembrolizumab before, during and after standard-of-care surgery had longer event-free survival without the cancer coming back and higher rates of substantial tumor shrinkage prior to surgery. The study was led by investigators from Dana-Farber Brigham Cancer Center and Washington University School of Medicine in St. Louis.

This new regimen represents a substantial change in workflow for head and neck cancer care, offering appropriate patients the option of receiving pembrolizumab before surgery for resectable locally advanced head and neck cancer.

“These findings represent a truly exciting time for our patients, as it is the first advance in this field in over two decades,” said Dr. Ravindra Uppaluri, the study’s overall principal investigator, director of Head and Neck Surgical Oncology at Dana-Farber and Brigham and Women’s Hospital, and Brigham and Women’s Hospital Endowed Chair in Otolaryngology.

“This is the first approval of a checkpoint inhibitor in the curative, perioperative setting and it represents a massive paradigm shift in how we manage surgically treated head and neck cancer going forward,” said Dr. Robert Haddad, chief of the Division of Head and Neck Oncology and the McGraw Chair in Head and Neck Oncology at Dana-Farber, professor of medicine at Harvard Medical School and the Dana-Farber Brigham Cancer Center principal investigator and member of the KEYNOTE-689 steering committee.

The KEYNOTE-689 trial randomized 714 patients with newly diagnosed stage 3 or stage 4A head and neck squamous cell cancer to receive either pembrolizumab before (called neoadjuvant), during and after (called adjuvant) standard of care or standard of care alone. The investigators also measured the presence of the target of pembrolizumab, PD-L1, in tumors to determine if higher scores of PD-L1 in tumors would affect response to treatment.

The study met its primary endpoint showing that patients who received pembrolizumab had longer event-free survival. Median event-free survival was 51.8 months with pembrolizumab and 30.4 without after a median of 38.3 months of follow-up. The team also observed significantly higher rates of major pathologic response, a substantial immune mediated tumor destruction seen in surgical resections.

The treatment was found to be safe with no new observed side effects. Further, patients taking pembrolizumab received surgery in a timely manner and were not delayed by immunotherapy-related side effects prior to surgery.

The data was previously presented at the 2025 American Association of Cancer Research (AACR) Annual Meeting.