Pembrolizumab Plus Standard of Care Receives Priority Review for Resectable Locally Advanced Head and Neck Cancer

The FDA granted priority review to pembrolizumab (Keytruda; Merck) for the treatment of patients with resectable, locally advanced head and neck squamous cell carcinoma (LA-HNSCC) as neoadjuvant treatment and continued as adjuvant treatment in combination with standard of care (SOC) radiotherapy with or without cisplatin (Platinol; Bristol Myers Squibb), followed by use as a single agent. The decision is based on positive data from the phase 3 KeyNOTE-689 trial (NCT03765918). The FDA set a PDUFA date of June 23, 2025.^1,2

Molecular model of pembrolizumab | Image Credit: © Dr_Microbe - stock.adobe.com

Cancers that develop in or near the throat, larynx, nose, sinuses, and mouth are referred to as HN cancer, which is estimated to have affected over 58,000 individuals in the United States in 2024 alone. Human papillomavirus and alcohol and tobacco use are 2 major factors that increase the risk of HN cancer. When it has spread outside of its original site but has not yet reached other sections of the body, it is known as LA-HNSCC.²

Pembrolizumab is a humanized monoclonal antibody that targets PD-1 to boost the body's immune system's capacity to combat tumor cells. By preventing PD-1 from interacting with its ligands, PD-L1 and PD-L2, pembrolizumab activates T lymphocytes, which can impact both tumor cells and healthy cells. It has received multiple approvals for various cancers, including non-small cell lung cancer, melanoma, and urothelial cancer, as well as HNSCC in combination with fluorouracil and platinum-based chemotherapy.^2,3

In the randomized, active-controlled, open-label phase 3 KEYNOTE-689 trial, 704 patients with resectable LA-HNSCC were randomized 1:1 to 2 groups. The first received 200 mg of pembrolizumab intravenously (IV every 3 weeks [Q3W] for 2 cycles) as neoadjuvant therapy prior to surgery, followed by pembrolizumab (200 mg IV Q3W for 15 cycles) plus of SOC radiotherapy with cisplatin (100 mg/m2IV Q3W for 3 cycles) as adjuvant therapy following surgery for high-risk patients or pembrolizumab (200 mg IV Q3W for 15 cycles) plus SOC radiotherapy without cisplatin as adjuvant therapy following surgery for low-risk patients.²

The second group had no neoadjuvant therapy prior to surgery, followed by either SOC radiotherapy with cisplatin (100 mg/m2IV Q3W for 3 cycles) as adjuvant therapy following surgery for high-risk patients or SOC radiotherapy without cisplatin as adjuvant therapy following surgery for low-risk patients.²

Pembrolizumab perioperative treatment yielded statistically significant improvements in the primary and secondary end points of event-free survival (EFS) and major pathological response (mPR), respectively, compared with adjuvant radiotherapy (with or without cisplatin) alone. The full data from the trial is to be presented at an upcoming medical conference.²

"The [SOC] for patients with resectable [LA-HNSCC] has remained the same for over 2 decades, representing a significant unmet need for new treatment options,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said in a news release. “Based on the compelling results of the KEYNOTE-689 trial, we hope to reduce the risk of recurrence and disease progression in earlier stages of disease.”²

REFERENCES

1. Study of pembrolizumab given prior to surgery and in combination with radiotherapy given post-surgery for advanced head and neck squamous cell carcinoma (MK-3475-689). Updated February 7, 2025. Accessed February 25, 2025. https://clinicaltrials.gov/study/NCT03765918

2. FDA G grants priority review to Merck’s Application for KEYTRUDA® (pembrolizumab) plus standard of care as perioperative treatment for resectable locally advanced head and neck squamous cell carcinoma. Merck. February 25, 2025. Accessed February 25, 2025. https://www.merck.com/news/fda-grants-priority-review-to-mercks-application-for-keytruda-pembrolizumab-plus-standard-of-care-as-perioperative-treatment-for-resectable-locally-advanced-head-and-neck-squamous-cel/

3. FDA-approved indications. Keytruda. Accessed February 25, 2025. https://www.keytruda.com/