FDA Approves Pembrolizumab for Perioperative Treatment of Head and Neck Cancer
The immunotherapy drug offers a new option for patients with resectable, locally advanced HNSCC.
WASHINGTON – The Food and Drug Administration (FDA) has granted approval to Pembrolizumab (Keytruda) for adult patients battling resectable, locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors exhibit PD-L1 expression. This drug is now indicated as a neoadjuvant treatment, followed by adjuvant treatment in conjunction with radiotherapy (RT), with or without cisplatin post-surgery, and then continued as a single agent. This decision marks the first FDA approval of a perioperative treatment strategy for locally advanced HNSCC.
The FDA’s decision was informed by data derived from the KEYNOTE-689 trial (NCT02358031), a randomized, multicenter, open-label study. Researchers assessed 714 HNSCC patients (Stage 3-4A), randomizing them (1:1) to either neoadjuvant Pembrolizumab every three weeks for two cycles, followed by adjuvant Pembrolizumab every three weeks for three cycles alongside RT, with or without cisplatin, and subsequently every three weeks for 12 cycles of Pembrolizumab as a single agent, or no neoadjuvant treatment before surgery, followed by adjuvant RT with or without cisplatin.
The trial’s primary endpoint was event-free survival (EFS), defined as the time from randomization until the first instance of disease progression preventing definitive surgery, local or distant disease progression or recurrence, or death from any cause. Overall survival (OS) served as the key secondary endpoint.
In patients whose tumors expressed PD-L1 CPS of 1 or greater (n = 682), median EFS reached 59.7 months (95% CI: 37.9, not reached) with Pembrolizumab, compared to 29.6 months (95% CI: 19.5, 41.9) in the control group (HR 0.70; 95% CI: 0.55-0.89; P = 0.00140). While OS data remained immature-representing 76% of pre-specified events-no indication of harm was observed within the CPS 1 or greater subgroup.
Impact and Future Implications
The approval of Pembrolizumab represents a substantial advancement in treating patients with resectable locally advanced HNSCC, providing the first perioperative immunotherapy option for this patient group. The KEYNOTE-689 trial advocates for integrating immunotherapy into earlier treatment stages. As OS data continues to mature, these findings suggest a promising new standard of care.
“The approval of pembrolizumab marks a important advance in the treatment landscape for patients with resectable locally advanced HNSCC…”
Understanding Head and Neck Squamous Cell Carcinoma (HNSCC)
Frequently Asked Questions About Pembrolizumab and HNSCC
- What is Pembrolizumab?
- Pembrolizumab is an immunotherapy drug that helps the body’s immune system fight cancer cells. It is indeed a monoclonal antibody that blocks the interaction between PD-1 and PD-L1, proteins that inhibit the immune response.
- how is Pembrolizumab used in HNSCC treatment?
- In HNSCC, Pembrolizumab is used as a neoadjuvant treatment (before surgery) and an adjuvant treatment (after surgery) in combination with radiotherapy and sometimes chemotherapy. It is also continued as a single agent after these treatments.
- What were the main findings of the KEYNOTE-689 trial?
- The KEYNOTE-689 trial found that patients with resectable, locally advanced HNSCC who received Pembrolizumab had significantly improved event-free survival compared to those who did not receive the drug.
