The European Medicine’s Agency has approved two new regimens of MSD’s KEYTRUDA (pembrolizumab) as first-line treatment for metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC).

MSD has announced that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, for the first-line treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 (combined positive score [CPS] ?1).

This approval is based on findings from the pivotal Phase 3 KEYNOTE-048 trial, in which KEYTRUDA, compared with standard treatment (cetuximab with carboplatin or cisplatin plus 5-FU), demonstrated a significant improvement in overall survival (OS) as monotherapy (HR = 0.74 [95% CI, (0.61-0.90); p=0.00133] and in combination with chemotherapy (HR=0.65 [95% CI, 0.53-0.80]; p=0.00002), in patients whose tumors expressed PD-L1 (CPS ?1).

This approval allows marketing of the KEYTRUDA monotherapy and combination regimen in all 28 EU member states plus Iceland, Lichtenstein and Norway.

David Peacock, Managing Director, MSD UK and Ireland, said: “Current treatment options for people with metastatic or unresectable recurrent head and neck squamous cell carcinoma are limited. We are very pleased to be able to offer two new treatment options which have the potential to address the unmet need in this devastating form of cancer. We are committed to working closely with NICE and the NHS so patients will soon be able to gain access. At MSD, innovation is at the forefront of everything we do and we continue to strive towards improvements in outcomes for cancer patients.”

This approval is based on data from the Phase 3 KEYNOTE-048 trial, a multi-center, randomised, open-label, active-controlled trial conducted in 882 patients with histologically confirmed metastatic or recurrent HNSCC of the oral cavity, pharynx or larynx, who had not previously received systemic therapy for recurrent or metastatic disease and who were considered incurable by local therapies. Randomisation was stratified by tumor PD-L1 expression (Tumor Proportion Score [TPS] ?50% or <50%), HPV status (positive or negative), and ECOG Performance Status (PS) (0 vs. 1). The dual primary endpoints were OS and progression-free survival (PFS).

Patients were randomised 1:1:1 to one of the following treatment arms:

• KEYTRUDA 200 mg intravenously every three weeks;
• KEYTRUDA 200 mg intravenously every three weeks, carboplatin AUC 5 mg/mL/min intravenously every three weeks or cisplatin 100 mg/m2 intravenously every three weeks and 5-FU 1000 mg/m2/day as a continuous intravenous infusion over 96 hours every three weeks (maximum of six cycles of platinum and 5-FU);
• Cetuximab 400 mg/m2 intravenously as the initial dose then 250 mg/m2 intravenously once weekly, carboplatin AUC 5 mg/mL/min intravenously every three weeks or cisplatin 100 mg/m2 intravenously every three weeks and 5-FU 1000 mg/m2/day as a continuous intravenous infusion over 96 hours every three weeks (maximum of six cycles of platinum and 5-FU).

Treatment with KEYTRUDA continued until RECIST v1.1-defined progression of disease as determined by the investigator, unacceptable toxicity or a maximum of 24 months.