Combining Pembrolizumab with Standard Chemoradiotherapy to Treat Head and Neck Squamous Cell Carcinoma
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on July 25th, 2025
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There had been limited advancements in the effort to improve the treatment of resectable locally advanced head and neck squamous cell carcinoma (HNSCC). The current standard therapy of radiation and cisplatin are ineffective and fail to prevent disease relapse in a significant amount of patients. Pembrolizumab had been proven to be effective at treating metastatic and recurrent HNSCC; thus, Merck funded a study to explore the possibility of adapting pembrolizumab to an earlier disease stage.
The phase 3 clinical trial included 714 participants with an average age of 60 years old who had recently been diagnosed with localized head and neck squamous cell carcinoma. Primary tumors can be detected in the oral cavity of 60% of the cohort. Tumor biopsy was performed to evaluate the degree of PD-1L expression, with only around 4% of the patients having an expression percentage less than 1%.
Depending on the treatment group which the patients were randomly assigned to, they will receive infusions of either placebo or 200 mg of pembrolizumab. This neoadjuvant infusion includes 2 rounds separated by 3 weeks. Afterward surgery will be performed to resect the tumor. Based on the degree of nodal extension of the tumor, patients with a lower risk of disease recurrence are then exposed to a radiotherapy regimen with a total dosage of 60 Gy. For patients with a higher risk of disease recurrence had their total radiation dosage upped to 66 Gy in combination with 3 rounds of cisplatin infusion at a dose of 100 mg per square meter of body surface area.
Either placebo or pembrolizumab at a dose of 200 mg was also used after surgery. Infusions were performed every three weeks for a total of 12 cycles. Pembrolizumab is an inhibitor that interferes with the interaction between PDL1 and the PD-1 receptor. This prevents the immunosuppressive effect that tumor can induce to avoid clearance by immune cells. After 36 months the researchers found that pembrolizumab helped prevent the risk of disease recurrence, progression or death by 34%. Adverse event analysis found that pembrolizumab was associated with a higher frequency of immune-mediated toxicity.
The phase 3 clinical trial included 714 participants with an average age of 60 years old who had recently been diagnosed with localized head and neck squamous cell carcinoma. Primary tumors can be detected in the oral cavity of 60% of the cohort. Tumor biopsy was performed to evaluate the degree of PD-1L expression, with only around 4% of the patients having an expression percentage less than 1%.
Depending on the treatment group which the patients were randomly assigned to, they will receive infusions of either placebo or 200 mg of pembrolizumab. This neoadjuvant infusion includes 2 rounds separated by 3 weeks. Afterward surgery will be performed to resect the tumor. Based on the degree of nodal extension of the tumor, patients with a lower risk of disease recurrence are then exposed to a radiotherapy regimen with a total dosage of 60 Gy. For patients with a higher risk of disease recurrence had their total radiation dosage upped to 66 Gy in combination with 3 rounds of cisplatin infusion at a dose of 100 mg per square meter of body surface area.
Either placebo or pembrolizumab at a dose of 200 mg was also used after surgery. Infusions were performed every three weeks for a total of 12 cycles. Pembrolizumab is an inhibitor that interferes with the interaction between PDL1 and the PD-1 receptor. This prevents the immunosuppressive effect that tumor can induce to avoid clearance by immune cells. After 36 months the researchers found that pembrolizumab helped prevent the risk of disease recurrence, progression or death by 34%. Adverse event analysis found that pembrolizumab was associated with a higher frequency of immune-mediated toxicity.